Skip to main content

Advertisement

SpringerLink
Log in

Region-specific vascular remodeling and its prevention by artificial gravity in weightless environment

  • Invited Review
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Evidence from recent ground and spaceflight studies with animals and humans supports the notion that microgravity-induced vascular remodeling contributes to postflight orthostatic intolerance. In the vascular beds of lower body, such as in splanchnic and lower limb circulation, resistance vessels would undergo hypotrophy and decrement in myogenic tone and vasoreactivity. Thus, despite the concurrent sympathetic activation, the increase in peripheral vascular resistance would still be compromised while astronauts were re-exposed to Earth’s 1-G gravity, since ~75 % of the total vascular conductance lies below the heart. On the contrary, cerebral arteries would undergo hypertrophy and vasoreactivity enhancement due to adaptation to cerebral hypertension, which protects the down-stream microcirculation in the brain during spaceflight. However, the enhanced vasoreactivity of cerebral vessels might also aggravate postflight orthostatic intolerance, particularly after long-duration spaceflight. Animal studies have indicated that the underlying mechanisms may involve ion-channel remodeling in vascular smooth muscle cells and vascular NO-NOS and local renin–angiotensin system (L-RAS). Furthermore, vascular remodeling and associated ion-channel and L-RAS changes can be prevented by a countermeasure of daily short-duration restoring to normal standing posture. These findings substantiate in general the hypothesis that redistribution of transmural pressure along the arterial vasculature due to the removal of gravity might be the primary factor that initiates vascular remodeling in microgravity, and daily short-duration restoring its normal distribution by intermittent artificial gravity (IAG) can effectively prevent the vascular adaptation and hence postflight cardiovascular deconditioning. IAG might also be beneficial in maintaining vascular health during future long-duration space flight.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Arbeille P, Achaibou F, Fomina G, Pottier JM, Porcher M (1996) Regional blood flow in microgravity: adaptation and deconditioning. Med Sci Sports Exerc 28(10 Suppl):S70–S79

    PubMed  CAS  Google Scholar 

  • Arbeille PP, Besnard SS, Kerbeci PP, Mohty DM (2005) Portal vein cross-sectional area and flow and orthostatic tolerance: a 90-day bed rest study. J Appl Physiol 99(5):1853–1857

    PubMed  Google Scholar 

  • Arbeille P, Kerbeci P, Mattar L, Shoemaker JK, Hughson R (2008) Insufficient flow reduction during LBNP in both splanchnic and lower limb areas is associated with orthostatic intolerance after bedrest. Am J Physiol Heart Circ Physiol 295(5):H1846–H1854

    PubMed  CAS  Google Scholar 

  • Baevsky RM, Baranov VM, Funtova II, Diedrich A, Pashenko AV, Chernikova AG, Drescher J, Jordan J, Tank J (2007) Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station. J Appl Physiol 103(1):156–161

    PubMed  Google Scholar 

  • Baker ES, Barratt MR, Wear ML (2008) Human response to space flight. In: Barratt MR, Pool SL (eds) Principles of clinical medicine for space flight. Springer Science+Business Media, NY, pp 27–57

    Google Scholar 

  • Bao JX, Zhang LF, Ma J (2007) Angiotensinogen and AT1R expression in cerebral and femoral arteries during hindlimb unloading in rats. Aviat Space Environ Med 78(9):852–858

    PubMed  CAS  Google Scholar 

  • Baranov VM, Tikhonov MA, Kotov AN, Kolesnikov VI (2000) Some mechanisms of modeling the hydrostatic component of hemodynamics in microgravity. Aviakosm Ekolog Med 34(4):27–31

    PubMed  CAS  Google Scholar 

  • Bayorh MA, Socci RR, Wang M, Emmett N, Thierry-Palmer M (2000) Salt-loading and simulated microgravity on baroreflex responsiveness in rats. J Gravit Physiol 7(3):23–29

    PubMed  CAS  Google Scholar 

  • Bayorh MA, Eatman D, Wang M, Socci RR, Emmett N, Thierry-Palmer M (2001) Indomethacin attenuates post-suspension hypotension in Sprague-Dawley rats. J Gravit Physiol 8(2):77–83

    PubMed  CAS  Google Scholar 

  • Behnke BJ, Zawieja DC, Gashev AA, Ray CA, Delp MD (2008) Diminished mesenteric vaso- and venoconstriction and elevated plasma ANP and BNP with simulated microgravity. J Appl Physiol 104(5):1273–1280

    PubMed  CAS  Google Scholar 

  • Berk BC (2001) Vascular smooth muscle growth: autocrine growth mechanisms. Physiol Rev 81(3):999–1030

    PubMed  CAS  Google Scholar 

  • Blaber AP, Goswami N, Bondar RL, Kassam MS (2011) Impairment of cerebral blood flow regulation in astronauts with orthostatic intolerance after flight. Stroke 42(7):1844–1850

    PubMed  Google Scholar 

  • Blacher J, Asmar R, Djane S, London GM, Safar ME (1999) Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 33(5):1111–1117

    PubMed  CAS  Google Scholar 

  • Bleeker MW, De Groot PC, Rongen GA, Rittweger J, Felsenberg D, Smits P, Hopman MT (2005) Vascular adaptation to deconditioning and the effect of an exercise countermeasure: results of the Berlin Bed Rest study. J Appl Physiol 99(4):1293–1300

    PubMed  Google Scholar 

  • Blomqvist CG (1996) Regulation of the systemic circulation at microgravity and during readaptation to 1G. Med Sci Sports Exerc 28(10 Suppl):S9–S13

    PubMed  CAS  Google Scholar 

  • Blomqvist CG, Stone HL (1983) Handbook of physiology. In: Shepherd JT, Abboud FM (eds) The cardiovascular system, vol 3. vol part 2. American Physiological Society, Bethesda, pp 1025–1063

  • Blomqvist CG, Buckey JC, Gaffney FA, Lane LD, Levine BD, Watenpaugh DE (1994) Mechanisms of post-flight orthostatic intolerance. J Gravit Physiol 1(1):P122–P124

    PubMed  CAS  Google Scholar 

  • Brizzee BL, Walker BR (1990) Altered baroreflex function after tail suspension in the conscious rat. J Appl Physiol 69(6):2091–2096

    PubMed  CAS  Google Scholar 

  • Broskey J, Sharp MK (2007) Evaluation of mechanisms of postflight orthostatic intolerance with a simple cardiovascular system model. Ann Biomed Eng 35(10):1800–1811

    PubMed  Google Scholar 

  • Buckey JC, Homick JL (2003) Standing after spaceflight: the effects of weightlessness on blood pressure. In: Buckey JC, Homick JL (eds) The Neurolab Spacelab Mission: Neuroscience Research in Space. NASA SP-2003-535, Houston, pp 171–172

  • Buckey JC Jr, Gaffney FA, Lane LD, Levine BD, Watenpaugh DE, Wright SJ, Yancy CW Jr, Meyer DM, Blomqvist CG (1996a) Central venous pressure in space. J Appl Physiol 81(1):19–25

    PubMed  Google Scholar 

  • Buckey JC Jr, Lane LD, Levine BD, Watenpaugh DE, Wright SJ, Moore WE, Gaffney FA, Blomqvist CG (1996b) Orthostatic intolerance after spaceflight. J Appl Physiol 81(1):7–18

    PubMed  Google Scholar 

  • Bund SJ, Lee RM (2003) Arterial structural changes in hypertension: a consideration of methodology, terminology and functional consequence. J Vasc Res 40(6):547–557

    PubMed  Google Scholar 

  • Burton RR, Meeker LJ (1997) Taking gravity into space. J Gravit Physiol 4(2):P17–P20

    PubMed  CAS  Google Scholar 

  • Buus NH, Kahr O, Mulvany MJ (1999) Effect of short- and long-term heart failure on small artery morphology and endothelial function in the rat. J Cardiovasc Pharmacol 34(1):34–40

    PubMed  CAS  Google Scholar 

  • Caiozzo VJ, Rose-Gottron C, Baldwin KM, Cooper D, Adams G, Hicks J, Kreitenberg A (2004) Hemodynamic and metabolic responses to hypergravity on a human-powered centrifuge. Aviat Space Environ Med 75(2):101–108

    PubMed  Google Scholar 

  • Christensen NJ, Heer M, Ivanova K, Norsk P (2005) Sympathetic nervous activity decreases during head-down bed rest but not during microgravity. J Appl Physiol 99(4):1552–1557

    PubMed  Google Scholar 

  • Chuong CJ, Fung YC (1986) On residual stresses in arteries. J Biomech Eng 108(2):189–192

    PubMed  CAS  Google Scholar 

  • Clement G, Pavy-Le Traon A (2004) Centrifugation as a countermeasure during actual and simulated microgravity: a review. Eur J Appl Physiol 92(3):235–248

    PubMed  CAS  Google Scholar 

  • Coats P, Hillier C (1999) Determination of an optimal axial-length tension for the study of isolated resistance arteries on a pressure myograph. Exp Physiol 84(6):1085–1094

    PubMed  CAS  Google Scholar 

  • Coats BW, Sharp MK (2010) Simulated stand tests and centrifuge training to prevent orthostatic intolerance on Earth, moon, and Mars. Ann Biomed Eng 38(3):1119–1131

    PubMed  Google Scholar 

  • Colleran PN, Wilkerson MK, Bloomfield SA, Suva LJ, Turner RT, Delp MD (2000) Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling. J Appl Physiol 89(3):1046–1054

    PubMed  CAS  Google Scholar 

  • Colleran PN, Behnke BJ, Wilkerson MK, Donato AJ, Delp MD (2008) Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca(2+) release mechanism. Am J Physiol Regul Integr Comp Physiol 294(5):R1577–R1585

    PubMed  CAS  Google Scholar 

  • Convertino VA (2002) Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures. J Gravit Physiol 9(2):1–13

    PubMed  Google Scholar 

  • Convertino VA (2009) Status of cardiovascular issues related to space flight: implications for future research directions. Respir Physiol Neurobiol 169(Suppl 1):S34–S37

    PubMed  Google Scholar 

  • Convertino VA, Cooke WH (2005) Evaluation of cardiovascular risks of spaceflight does not support the NASA bioastronautics critical path roadmap. Aviat Space Environ Med 76(9):869–876

    PubMed  Google Scholar 

  • Cooke WH, Ames JI, Crossman AA, Cox JF, Kuusela TA, Tahvanainen KU, Moon LB, Drescher J, Baisch FJ, Mano T, Levine BD, Blomqvist CG, Eckberg DL (2000) Nine months in space: effects on human autonomic cardiovascular regulation. J Appl Physiol 89(3):1039–1045

    PubMed  CAS  Google Scholar 

  • Coupe M, Fortrat JO, Larina I, Gauquelin-Koch G, Gharib C, Custaud MA (2009) Cardiovascular deconditioning: from autonomic nervous system to microvascular dysfunctions. Respir Physiol Neurobiol 169(Suppl 1):S10–S12

    PubMed  Google Scholar 

  • Cox JF, Tahvanainen KU, Kuusela TA, Levine BD, Cooke WH, Mano T, Iwase S, Saito M, Sugiyama Y, Ertl AC, Biaggioni I, Diedrich A, Robertson RM, Zuckerman JH, Lane LD, Ray CA, White RJ, Pawelczyk JA, Buckey JC Jr, Baisch FJ, Blomqvist CG, Robertson D, Eckberg DL (2002) Influence of microgravity on astronauts’ sympathetic and vagal responses to Valsalva’s manoeuvre. J Physiol 538(Pt 1):309–320

    PubMed  CAS  Google Scholar 

  • Dabire H, Mestivier D, Jarnet J, Safar ME, Chau NP (1998) Quantification of sympathetic and parasympathetic tones by nonlinear indexes in normotensive rats. Am J Physiol 275(4 Pt 2):H1290–H1297

    PubMed  CAS  Google Scholar 

  • Deavers DR, Musacchia XJ, Meininger GA (1980) Model for antiorthostatic hypokinesia: head-down tilt effects on water and salt excretion. J Appl Physiol 49(4):576–582

    PubMed  CAS  Google Scholar 

  • Delp MD (1999) Myogenic and vasoconstrictor responsiveness of skeletal muscle arterioles is diminished by hindlimb unloading. J Appl Physiol 86(4):1178–1184

    PubMed  CAS  Google Scholar 

  • Delp MD, Holder-Binkley T, Laughlin MH, Hasser EM (1993) Vasoconstrictor properties of rat aorta are diminished by hindlimb unweighting. J Appl Physiol 75(6):2620–2628

    PubMed  CAS  Google Scholar 

  • Delp MD, Brown M, Laughlin MH, Hasser EM (1995) Rat aortic vasoreactivity is altered by old age and hindlimb unloading. J Appl Physiol 78(6):2079–2086

    Google Scholar 

  • Delp MD, Colleran PN, Wilkerson MK, McCurdy MR, Muller-Delp J (2000) Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity. Am J Physiol Heart Circ Physiol 278(6):H1866–H1873

    PubMed  CAS  Google Scholar 

  • Demiot C, Dignat-George F, Fortrat JO, Sabatier F, Gharib C, Larina I, Gauquelin-Koch G, Hughson R, Custaud MA (2007) WISE 2005: chronic bed rest impairs microcirculatory endothelium in women. Am J Physiol Heart Circ Physiol 293(5):H3159–H3164

    PubMed  CAS  Google Scholar 

  • Desplanches D, Mayet MH, Sempore B, Frutoso J, Flandrois R (1987) Effect of spontaneous recovery or retraining after hindlimb suspension on aerobic capacity. J Appl Physiol 63(5):1739–1743

    PubMed  CAS  Google Scholar 

  • di Prampero PE (2000) Cycling on Earth, in space, on the Moon. Eur J Appl Physiol 82(5–6):345–360

    PubMed  Google Scholar 

  • Ding ZP, Zhang LF, Chen J, Ma J (1993) Altered responsiveness of arterial baroreflex after 90-day simulated weightlessness in rats (in Chinese with English Abstract). Chin J Appl Physiol 9:300–304

    Google Scholar 

  • Dorfman TA, Levine BD, Tillery T, Peshock RM, Hastings JL, Schneider SM, Macias BR, Biolo G, Hargens AR (2007) Cardiac atrophy in women following bed rest. J Appl Physiol 103(1):8–16

    PubMed  Google Scholar 

  • Drummond GR, Selemidis S, Griendling KK, Sobey CG (2011) Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov 10(6):453–471

    PubMed  CAS  Google Scholar 

  • Dunbar SL, Berkowitz DE, Brooks-Asplund EM, Shoukas AA (2000) The effects of hindlimb unweighting on the capacitance of rat small mesenteric veins. J Appl Physiol 89(5):2073–2077

    PubMed  CAS  Google Scholar 

  • Dunn CD, Johnson PC, Lange RD (1986) Regulation of hematopoiesis in rats exposed to antiorthostatic hypokinetic/hypodynamia: II. Mechanisms of the “anemia”. Aviat Space Environ Med 57(1):36–44

    PubMed  CAS  Google Scholar 

  • Dyson KS, Arbeille P, Shoemaker JK, Custaud MA, Hughson RL (2007) WISE 2005: flow and nitroglycerin mediated dilation following 56 days of head down tilt bed rest with and without an exercise countermeasure. J Gravit Physiol 14(1):P55–P56

    PubMed  CAS  Google Scholar 

  • Ertl AC, Diedrich A, Biaggioni I, Levine BD, Robertson RM, Cox JF, Zuckerman JH, Pawelczyk JA, Ray CA, Buckey JC Jr, Lane LD, Shiavi R, Gaffney FA, Costa F, Holt C, Blomqvist CG, Eckberg DL, Baisch FJ, Robertson D (2002) Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space. J Physiol 538(Pt 1):321–329

    PubMed  CAS  Google Scholar 

  • Etter KE, Goswami N, Sharp MK (2011) Modelling of cardiovascular response to graded orthostatic stress: role of capillary filtration. Eur J Clin Invest 41(8):807–819

    PubMed  Google Scholar 

  • Evans JM, Stenger MB, Moore FB, Hinghofer-Szalkay H, Rossler A, Patwardhan AR, Brown DR, Ziegler MG, Knapp CF (2004) Centrifuge training increases presyncopal orthostatic tolerance in ambulatory men. Aviat Space Environ Med 75(10):850–858

    PubMed  Google Scholar 

  • Fagette S, Lo M, Gharib C, Gauquelin G (1995a) Cardiovascular variability and baroreceptor reflex sensitivity over a 14-day tail suspension in rats. J Appl Physiol 78(2):717–724

    PubMed  CAS  Google Scholar 

  • Fagette S, Somody L, Bouzeghrane F, Cottet-Emard JM, Gharib C, Gauquelin G (1995b) Central and peripheral sympathetic activities in rats during recovery from simulated weightlessness. J Appl Physiol 79(6):1991–1997

    PubMed  CAS  Google Scholar 

  • Faraci FM, Heistad DD (1990) Regulation of large cerebral arteries and cerebral microvascular pressure. Circ Res 66(1):8–17

    PubMed  CAS  Google Scholar 

  • Fischer D, Arbeille P, Shoemaker JK, O’Leary DD, Hughson RL (2007) Altered hormonal regulation and blood flow distribution with cardiovascular deconditioning after short-duration head down bed rest. J Appl Physiol 103(6):2018–2025

    PubMed  CAS  Google Scholar 

  • Fogarty JA, Otto C, Kerstman E, Oubre C, Wu J (2011) The Visual Impairment Intracranial Pressure Summit Report vol NASA/TP–2011-216160

  • Foley CM, Mueller PJ, Hasser EM, Heesch CM (2005) Hindlimb unloading and female gender attenuate baroreflex-mediated sympathoexcitation. Am J Physiol Regul Integr Comp Physiol 289(5):R1440–R1447

    PubMed  CAS  Google Scholar 

  • Folkow B (1987) Structure and function of the arteries in hypertension. Am Heart J 114(4 Pt 2):938–948

    PubMed  CAS  Google Scholar 

  • Folkow B, Svanborg A (1993) Physiology of cardiovascular aging. Physiol Rev 73(4):725–764

    PubMed  CAS  Google Scholar 

  • Fridez P, Rachev A, Meister JJ, Hayashi K, Stergiopulos N (2001) Model of geometrical and smooth muscle tone adaptation of carotid artery subject to step change in pressure. Am J Physiol Heart Circ Physiol 280 (6):H2752–H2760

    Google Scholar 

  • Fridez P, Makino A, Kakoi D, Miyazaki H, Meister JJ, Hayashi K, Stergiopulos N (2002) Adaptation of conduit artery vascular smooth muscle tone to induced hypertension. Ann Biomed Eng 30(7):905–916

    PubMed  CAS  Google Scholar 

  • Fritsch-Yelle JM, Charles JB, Jones MM, Wood ML (1996) Microgravity decreases heart rate and arterial pressure in humans. J Appl Physiol 80(3):910–914

    PubMed  CAS  Google Scholar 

  • Fu Q, Levine BD, Pawelczyk JA, Ertl AC, Diedrich A, Cox JF, Zuckerman JH, Ray CA, Smith ML, Iwase S, Saito M, Sugiyama Y, Mano T, Zhang R, Iwasaki K, Lane LD, Buckey JC Jr, Cooke WH, Robertson RM, Baisch FJ, Blomqvist CG, Eckberg DL, Robertson D, Biaggioni I (2002) Cardiovascular and sympathetic neural responses to handgrip and cold pressor stimuli in humans before, during and after spaceflight. J Physiol 544(Pt 2):653–664

    PubMed  CAS  Google Scholar 

  • Fu Q, Witkowski S, Levine BD (2004a) Vasoconstrictor reserve and sympathetic neural control of orthostasis. Circulation 110(18):2931–2937

    PubMed  Google Scholar 

  • Fu ZJ, Xie MJ, Zhang LF, Cheng HW, Ma J (2004b) Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity. Am J Physiol Heart Circ Physiol 287(4):H1505–H1515

    PubMed  CAS  Google Scholar 

  • Gabrielsen A, Norsk P (2007) Effect of spaceflight on the subcutaneous venoarteriolar reflex in the human lower leg. J Appl Physiol 103(3):959–962

    PubMed  Google Scholar 

  • Gao F, Bao JX, Xue JH, Huang J, Huang WQ, Wu SX, Zhang LF (2009) Regional specificity of adaptation change in large elastic arteries of simulated microgravity rats. Acta Physiol Hung 96(2):167–187

    PubMed  CAS  Google Scholar 

  • Gao F, Cheng JH, Bai YG, Boscolo M, Huang XF, Zhang X, Zhang LF (2012a) Mechanical properties and composition of mesenteric small arteries of simulated microgravity rats with and without daily–Gx graviation. Acta Physiol Sinica 64:107–120

    PubMed  Google Scholar 

  • Gao F, Cheng JH, Xue JH, Bai YG, Chen MS, Huang WQ, Huang J, Wu SX, Han HC, Zhang LF (2012b) In vivo and ex vivo studies on region-specific remodeling of large elastic arteries due to simulated weightlessness and its prevention by gravity-based countermeasure. Acta Physiologica Sinica 64(1):14–26

    PubMed  CAS  Google Scholar 

  • Gashev AA, Delp MD, Zawieja DC (2006) Inhibition of active lymph pump by simulated microgravity in rats. Am J Physiol Heart Circ Physiol 290(6):H2295–H2308

    PubMed  CAS  Google Scholar 

  • Gazenko OG, Genin AM, Egorov AD (1981) Summary of medical investigations in the U.S.S.R. manned space missions. Acta Astronaut 8(9–10):907–917

    PubMed  CAS  Google Scholar 

  • Geary GG, Krause DN, Purdy RE, Duckles SP (1998) Simulated microgravity increases myogenic tone in rat cerebral arteries. J Appl Physiol 85(5):1615–1621

    PubMed  CAS  Google Scholar 

  • Gotoh TM, Fujiki N, Tanaka K, Matsuda T, Gao S, Morita H (2004) Acute hemodynamic responses in the head during microgravity induced by free drop in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 286(6):R1063–R1068

    PubMed  CAS  Google Scholar 

  • Guinet P, Schneider SM, Macias BR, Watenpaugh DE, Hughson RL, Le Traon AP, Bansard JY, Hargens AR (2009) WISE-2005: effect of aerobic and resistive exercises on orthostatic tolerance during 60 days bed rest in women. Eur J Appl Physiol 106(2):217–227

    PubMed  Google Scholar 

  • Gundel A, Drescher J, Spatenko YA, Polyakov VV (2002) Changes in basal heart rate in spaceflights up to 438 days. Aviat Space Environ Med 73(1):17–21

    PubMed  Google Scholar 

  • Gurovsky NN, Gazenko OG, Adamovich BA, Ilyin EA, Genin AM, Korolkov VI, Shipov AA, Kotovskaya AR, Kondratyeva VA, Serova LV, Kondratyev YuI (1980) Study of physiological effects of weightlessness and artificial gravity in the flight of the biosatellite Cosmos-936. Acta Astronaut 7(1):113–121

    PubMed  CAS  Google Scholar 

  • Hargens AR, Richardson S (2009) Cardiovascular adaptations, fluid shifts, and countermeasures related to space flight. Respir Physiol Neurobiol 169(Suppl 1):S30–S33

    PubMed  Google Scholar 

  • Hargens AR, Watenpaugh DE (1996) Cardiovascular adaptation to spaceflight. Med Sci Sports Exerc 28(8):977–982

    PubMed  CAS  Google Scholar 

  • Hargens A, Steskal J, Johansson C, Tipton C (1984) Tissue fluid shift, forelimb loading, and tail tension in tail-suspended rats. Physiologist 27:S37–S38

    Google Scholar 

  • Hasser EM, Moffitt JA (2001) Regulation of sympathetic nervous system function after cardiovascular deconditioning. Ann N Y Acad Sci 940:454–468

    PubMed  CAS  Google Scholar 

  • Hastings JL, Krainski F, Snell PG, Pacini EL, Jain M, Bhella PS, Shibata S, Fu Q, Palmer MD, Levine BD (2012) Effect of rowing ergometry and oral volume loading on cardiovascular structure and function during bed rest. J Appl Physiol 112(10):1735–1743

    PubMed  Google Scholar 

  • Hatton DC, Yue Q, Chapman J, Xue H, Dierickx J, Roullet C, Coste S, Roullet JB, McCarron DA (2002) Blood pressure and mesenteric resistance arterial function after spaceflight. J Appl Physiol 92(1):13–17

    PubMed  CAS  Google Scholar 

  • Heldt T, Shim EB, Kamm RD, Mark RG (2002) Computational modeling of cardiovascular response to orthostatic stress. J Appl Physiol 92(3):1239–1254

    PubMed  Google Scholar 

  • Herault S, Fomina G, Alferova I, Kotovskaya A, Poliakov V, Arbeille P (2000) Cardiac, arterial and venous adaptation to weightlessness during 6-month MIR spaceflights with and without thigh cuffs (bracelets). Eur J Appl Physiol 81(5):384–390

    PubMed  CAS  Google Scholar 

  • Hesse C, Siedler H, Luntz SP, Arendt BM, Goerlich R, Fricker R, Heer M, Haefeli WE (2005) Modulation of endothelial and smooth muscle function by bed rest and hypoenergetic, low-fat nutrition. J Appl Physiol 99(6):2196–2203

    PubMed  Google Scholar 

  • Hughson RL (2009) Recent findings in cardiovascular physiology with space travel. Respir Physiol Neurobiol 169(Suppl 1):S38–S41

    PubMed  Google Scholar 

  • Hughson RL, Shoemaker JK, Arbeille P, Dyson KS, Edgell H, Kerbeci P, Mattar L, Zuj K, Greaves DK (2007) WISE 2005: vascular responses to 60-day bed rest in women. J Gravit Physiol 14(1):P53–P54

    PubMed  CAS  Google Scholar 

  • Hwang S, Shelkovnikov SA, Purdy RE (2007) Simulated microgravity effects on the rat carotid and femoral arteries: role of contractile protein expression and mechanical properties of the vessel wall. J Appl Physiol 102(4):1595–1603

    PubMed  CAS  Google Scholar 

  • Iwasaki K, Levine BD, Zhang R, Zuckerman JH, Pawelczyk JA, Diedrich A, Ertl AC, Cox JF, Cooke WH, Giller CA, Ray CA, Lane LD, Buckey JC Jr, Baisch FJ, Eckberg DL, Robertson D, Biaggioni I, Blomqvist CG (2007) Human cerebral autoregulation before, during and after spaceflight. J Physiol 579(Pt 3):799–810

    PubMed  CAS  Google Scholar 

  • Jacobsen JC, Mulvany MJ, Holstein-Rathlou NH (2008) A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation. Am J Physiol Regul Integr Comp Physiol 294(4):R1379–R1389

    PubMed  CAS  Google Scholar 

  • Jasperse JL, Woodman CR, Price EM, Hasser EM, Laughlin MH (1999) Hindlimb unweighting decreases ecNOS gene expression and endothelium-dependent dilation in rat soleus feed arteries. J Appl Physiol 87(4):1476–1482

    PubMed  CAS  Google Scholar 

  • Katkov VE, Chestukhin VV (1980) Blood pressure and oxygenation in different cardiovascular compartments of a normal man during postural exposures. Aviat Space Environ Med 51(11):1234–1242

    PubMed  CAS  Google Scholar 

  • Kotovskaia AR (2008) The problem of artificial gravity: the present status and possible approaches. Aviakosm Ekolog Med 42(6):74–83

    PubMed  CAS  Google Scholar 

  • Kotovskaia AR, Fomina GA (2010) The features of adaptation and disadaptation of the human cardiovascular system in the space flight conditions. Fiziol Cheloveka 36(2):78–86

    PubMed  CAS  Google Scholar 

  • Kramer LA, Sargsyan AE, Hasan KM, Polk JD, Hamilton DR (2012) Orbital and Intracranial Effects of Microgravity: findings at 3-T MR Imaging. Radiology 263(3):819–827

    PubMed  Google Scholar 

  • Kreitenberg A, Baldwin KM, Bagian JP, Cotten S, Witmer J, Caiozzo VJ (1998) The “Space Cycle” Self Powered Human Centrifuge: a proposed countermeasure for prolonged human spaceflight. Aviat Space Environ Med 69(1):66–72

    PubMed  CAS  Google Scholar 

  • Kvetnansky R, Noskov VB, Blazicek P, Gharib C, Popova IA, Gauquelin G, Macho L, Guell A, Grigoriev AI (1991) Activity of the sympathoadrenal system in cosmonauts during 25-day space flight on station Mir. Acta Astronaut 23:109–116

    PubMed  CAS  Google Scholar 

  • Lakatta EG (1993) Cardiovascular regulatory mechanisms in advanced age. Physiol Rev 73(2):413–467

    PubMed  CAS  Google Scholar 

  • Lakin WD, Stevens SA, Penar PL (2007) Modeling intracranial pressures in microgravity: the influence of the blood-brain barrier. Aviat Space Environ Med 78(10):932–936

    PubMed  Google Scholar 

  • Leach CS, Rambaut PC (1977) Biomedical responses of the Skylab crewmen: an overview. Biomedical results from Skylab

  • Leach CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, Smith SM, Lane HW, Krauhs JM (1996) Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol 81(1):105–116

    PubMed  CAS  Google Scholar 

  • Lee SM, Schneider SM, Boda WL, Watenpaugh DE, Macias BR, Meyer RS, Hargens AR (2007) Supine LBNP exercise maintains exercise capacity in male twins during 30-d bed rest. Med Sci Sports Exerc 39(8):1315–1326

    PubMed  Google Scholar 

  • Lee SM, Moore AD, Everett ME, Stenger MB, Platts SH (2010) Aerobic exercise deconditioning and countermeasures during bed rest. Aviat Space Environ Med 81(1):52–63

    PubMed  Google Scholar 

  • Lehoux S, Tedgui A (2003) Cellular mechanics and gene expression in blood vessels. J Biomech 36(5):631–643. pii:S0021929002004414

    Google Scholar 

  • Lehoux S, Castier Y, Tedgui A (2006) Molecular mechanisms of the vascular responses to haemodynamic forces. J Intern Med 259(4):381–392

    PubMed  CAS  Google Scholar 

  • Levine BD, Zuckerman JH, Pawelczyk JA (1997) Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance. Circulation 96(2):517–525

    PubMed  CAS  Google Scholar 

  • Levine BD, Pawelczyk JA, Ertl AC, Cox JF, Zuckerman JH, Diedrich A, Biaggioni I, Ray CA, Smith ML, Iwase S, Saito M, Sugiyama Y, Mano T, Zhang R, Iwasaki K, Lane LD, Buckey JC Jr, Cooke WH, Baisch FJ, Eckberg DL, Blomqvist CG (2002) Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight. J Physiol 538(Pt 1):331–340

    PubMed  CAS  Google Scholar 

  • Lin LJ, Gao F, Bai YG, Bao JX, Huang XF, Ma J, Zhang LF (2009) Contrasting effects of simulated microgravity with and without daily -Gx gravitation on structure and function of cerebral and mesenteric small arteries in rats. J Appl Physiol 107(6):1710–1721

    PubMed  Google Scholar 

  • Looft-Wilson RC, Gisolfi CV (2000) Rat small mesenteric artery function after hindlimb suspension. J Appl Physiol 88(4):1199–1206

    PubMed  CAS  Google Scholar 

  • Ma J, Kahwaji CI, Ni Z, Vaziri ND, Purdy RE (2003) Effects of simulated microgravity on arterial nitric oxide synthase and nitrate and nitrite content. J Appl Physiol 94(1):83–92

    PubMed  CAS  Google Scholar 

  • Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Tran D, Lipsky W, Choi J, Stern C, Kuyumjian R, Polk JD (2011) Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118(10):2058–2069

    PubMed  Google Scholar 

  • Mao QW, Zhang LF, Ma J, Zhang YQ, Huang WQ (2000) Plastic change in density of perivascular peptidergic nerve fibers around the cerebral arteries of rats during simulated weightlessness and its reversal. Acta Anatomica Sinica 31:124–128

    Google Scholar 

  • Martel E, Champeroux P, Lacolley P, Richard S, Safar M, Cuche JL (1996) Central hypervolemia in the conscious rat: a model of cardiovascular deconditioning. J Appl Physiol 80(4):1390–1396

    PubMed  CAS  Google Scholar 

  • Martinez-Lemus LA, Hill MA, Meininger GA (2009) The plastic nature of the vascular wall: a continuum of remodeling events contributing to control of arteriolar diameter and structure. Physiology (Bethesda) 24:45–57

    Google Scholar 

  • Matsumoto T, Hayashi K (1996) Stress and strain distribution in hypertensive and normotensive rat aorta considering residual strain. J Biomech Eng 118(1):62–73

    PubMed  CAS  Google Scholar 

  • McDonald KS, Delp MD, Fitts RH (1992) Effect of hindlimb unweighting on tissue blood flow in the rat. J Appl Physiol 72(6):2210–2218

    PubMed  CAS  Google Scholar 

  • Meck JV, Waters WW, Ziegler MG, deBlock HF, Mills PJ, Robertson D, Huang PL (2004) Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic receptor responses before flight and central autonomic dysregulation postflight. Am J Physiol Heart Circ Physiol 286(4):H1486–H1495

    PubMed  CAS  Google Scholar 

  • Mehta PK, Griendling KK (2007) Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 292(1):C82–C97

    PubMed  CAS  Google Scholar 

  • Moffitt JA, Foley CM, Schadt JC, Laughlin MH, Hasser EM (1998) Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats. Am J Physiol 274(5 Pt 2):R1397–R1405

    PubMed  CAS  Google Scholar 

  • Moffitt JA, Heesch CM, Hasser EM (2002) Increased GABA(A) inhibition of the RVLM after hindlimb unloading in rats. Am J Physiol Regul Integr Comp Physiol 283(3):R604–R614

    PubMed  CAS  Google Scholar 

  • Monos E, Raffai G, Dörnyei G, Nádasy GL, Fehér E (2006) Structural and functional responses of extremity veins to long-term gravitational loading or unloading—lesson from animal systerms. Acta Astronaut 60:406–414

    Google Scholar 

  • Moore ST, Diedrich A, Biaggioni I, Kaufmann H, Raphan T, Cohen B (2005) Artificial gravity: a possible countermeasure for post-flight orthostatic intolerance. Acta Astronaut 56(9–12):867–876

    PubMed  Google Scholar 

  • Morey-Holton ER, Globus RK (2002) Hindlimb unloading rodent model: technical aspects. J Appl Physiol 92(4):1367–1377

    PubMed  Google Scholar 

  • Morey-Holton E, Globus RK, Kaplansky A, Durnova G (2005) The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data. In: Sonnenfeld G (ed) Experimentation with animal models in space. 2005/08/17 edn. Elsevier B.V., Amsterdam, pp 7–40

  • Mueller PJ, Foley CM, Hasser EM (2005) Hindlimb unloading alters nitric oxide and autonomic control of resting arterial pressure in conscious rats. Am J Physiol Regul Integr Comp Physiol 289(1):R140–R147

    PubMed  CAS  Google Scholar 

  • Mueller PJ, Sullivan MJ, Grindstaff RR, Cunningham JT, Hasser EM (2006) Regulation of plasma vasopressin and renin activity in conscious hindlimb-unloaded rats. Am J Physiol Regul Integr Comp Physiol 291(1):R46–R52

    PubMed  CAS  Google Scholar 

  • Musacchia XJ, Fagette S (1997) Weightlessness simulations for cardiovascular and muscle systems: validity of rat models. J Gravit Physiol 4(3):49–59

    PubMed  CAS  Google Scholar 

  • Musacchia XJ, Steffen JM, Dombrowski J (1992) Rat cardiovascular responses to whole body suspension: head-down and non-head-down tilt. J Appl Physiol 73(4):1504–1509

    PubMed  CAS  Google Scholar 

  • Navasiolava N, Custaud MA (2009) What are the future top priority questions in cardiovascular research and what new hardware needs to be developed? Respir Physiol Neurobiol 169(Suppl 1):S73–S74

    PubMed  Google Scholar 

  • Norsk P (2009) Cardiovascular research in space. Respir Physiol Neurobiol 169(Suppl 1):S2–S3

    PubMed  Google Scholar 

  • Norsk P, Christensen NJ (2009) The paradox of systemic vasodilatation and sympathetic nervous stimulation in space. Respir Physiol Neurobiol 169(Suppl 1):S26–S29

    PubMed  Google Scholar 

  • Norsk P, Drummer C, Rocker L, Strollo F, Christensen NJ, Warberg J, Bie P, Stadeager C, Johansen LB, Heer M et al (1995) Renal and endocrine responses in humans to isotonic saline infusion during microgravity. J Appl Physiol 78(6):2253–2259

    PubMed  CAS  Google Scholar 

  • Norsk P, Damgaard M, Petersen L, Gybel M, Pump B, Gabrielsen A, Christensen NJ (2006) Vasorelaxation in space. Hypertension 47(1):69–73

    PubMed  CAS  Google Scholar 

  • Overton JM, Tipton CM (1990) Effect of hindlimb suspension on cardiovascular responses to sympathomimetics and lower body negative pressure. J Appl Physiol 68(1):355–362

    PubMed  CAS  Google Scholar 

  • Overton JM, Woodman CR, Tipton CM (1989) Effect of hindlimb suspension on VO2 max and regional blood flow responses to exercise. J Appl Physiol 66(2):653–659

    PubMed  CAS  Google Scholar 

  • Papadopoulos A, Delp MD (2003) Effects of hindlimb unweighting on the mechanical and structure properties of the rat abdominal aorta. J Appl Physiol 94(2):439–445

    PubMed  Google Scholar 

  • Pavy-Le Traon A, Heer M, Narici MV, Rittweger J, Vernikos J (2007) From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol 101(2):143–194

    PubMed  CAS  Google Scholar 

  • Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist CG, Zerwekh JE, Peshock RM, Weatherall PT, Levine BD (2001) Cardiac atrophy after bed rest and spaceflight. J Appl Physiol 91(2):645–653

    PubMed  CAS  Google Scholar 

  • Pincus SM, Goldberger AL (1994) Physiological time-series analysis: what does regularity quantify? Am J Physiol 266(4 Pt 2):H1643–H1656

    PubMed  CAS  Google Scholar 

  • Platts SH, Martin DS, Stenger MB, Perez SA, Ribeiro LC, Summers R, Meck JV (2009) Cardiovascular adaptations to long-duration head-down bed rest. Aviat Space Environ Med 80(5 Suppl):A29–A36

    PubMed  Google Scholar 

  • Prewitt RL, Rice DC, Dobrian AD (2002) Adaptation of resistance arteries to increases in pressure. Microcirculation 9(4):295–304

    Google Scholar 

  • Prisby RD, Wilkerson MK, Sokoya EM, Bryan RM Jr, Wilson E, Delp MD (2006) Endothelium-dependent vasodilation of cerebral arteries is altered with simulated microgravity through nitric oxide synthase and EDHF mechanisms. J Appl Physiol 101(1):348–353

    PubMed  CAS  Google Scholar 

  • Prisk GK, Guy HJ, Elliott AR, Deutschman RA 3rd, West JB (1993) Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity. J Appl Physiol 75(1):15–26

    PubMed  CAS  Google Scholar 

  • Ren XL, Zhang R, Zhang YY, Liu H, Yu JW, Cai Y, Wang ZC, Purdy RE, Ma J (2011) Nitric oxide synthase activity in the abdominal aorta of rats is decreased after 4 weeks of simulated microgravity. Clin Exp Pharmacol Physiol 38(10):683–687

    PubMed  CAS  Google Scholar 

  • Rizzoni D, Porteri E, Boari GE, De Ciuceis C, Sleiman I, Muiesan ML, Castellano M, Miclini M, Agabiti-Rosei E (2003) Prognostic significance of small-artery structure in hypertension. Circulation 108(18):2230–2235

    PubMed  Google Scholar 

  • Rodionov IM, Timin EN, Matchkov VV, Tarasova OS, Vinogradova OL (1999) An experimental study and mathematical simulation of adrenergic control of hindlimb vessels in rats after 3-week tail suspension. Environ Med 43(1):1–9

    PubMed  CAS  Google Scholar 

  • Rowell LB (1993) Human cardiovascular control. Oxford University Press, New York

    Google Scholar 

  • Rowell LB, Detry JM, Blackmon JR, Wyss C (1972) Importance of the splanchnic vascular bed in human blood pressure regulation. J Appl Physiol 32(2):213–220

    PubMed  CAS  Google Scholar 

  • Schneider SM, Lee SM, Macias BR, Watenpaugh DE, Hargens AR (2009) WISE-2005: exercise and nutrition countermeasures for upright VO2 peak during bed rest. Med Sci Sports Exerc 41(12):2165–2176

    PubMed  Google Scholar 

  • Schrage WG, Woodman CR, Laughlin MH (2000) Hindlimb unweighting alters endothelium-dependent vasodilation and ecNOS expression in soleus arterioles. J Appl Physiol 89(4):1483–1490

    PubMed  CAS  Google Scholar 

  • Shellock FG, Swan HJ, Rubin SA (1985) Early central venous pressure changes in the rat during two different levels of head-down suspension. Aviat Space Environ Med 56(8):791–795

    PubMed  CAS  Google Scholar 

  • Sheriff DD, Nadland IH, Toska K (2010) Role of sympathetic responses on the hemodynamic consequences of rapid changes in posture in humans. J Appl Physiol 108(3):523–532

    PubMed  Google Scholar 

  • Shimizu T (1999) Development of the aortic baroreflex system under conditions of microgravity. J Gravit Physiol 6(1):P55–P58

    PubMed  CAS  Google Scholar 

  • Shimizu T, Yamasaki M, Waki H, Katsuda S-I, Oishi H, Katahira K, Nagayama T, Miyake M, Miyamoto Y (2003) Development of the aortic baroreflex in microgravity. In: Buckey JC, Homick JL (eds) The Neurolab Spacelab Mission: Neuroscience Research in Space. NASA SP-2003-535, pp 151–159

  • Shipov AA (1997) Artificial gravity. In: Nicogossian A, Mohler S, Gazenko O, Grigoriev A (eds) In: Space biology and medicine: humans in spaceflight, vol 3. vol book 2, 2nd edn. American Institute of Aeronautics and Astronautics, Reston, pp 349–363

  • Shiraishi M, Kamo T, Kamegai M, Baevsky RM, Funtova II, Chernikova A, Nemoto S, Hotta M, Nomura Y, Suzuki T (2004) Periodic structures and diurnal variation in blood pressure and heart rate in relation to microgravity on space station MIR. Biomed Pharmacother 58(Suppl 1):S31–S34

    PubMed  Google Scholar 

  • Shykoff BE, Farhi LE, Olszowka AJ, Pendergast DR, Rokitka MA, Eisenhardt CG, Morin RA (1996) Cardiovascular response to submaximal exercise in sustained microgravity. J Appl Physiol 81(1):26–32

    PubMed  CAS  Google Scholar 

  • Sides MB, Vernikos J, Convertino VA, Stepanek J, Tripp LD, Draeger J, Hargens AR, Kourtidou-Papadeli C, Pavy-LeTraon A, Russomano T, Wong JY, Buccello RR, Lee PH, Nangalia V, Saary MJ (2005) The Bellagio Report: cardiovascular risks of spaceflight: implications for the future of space travel. Aviat Space Environ Med 76(9):877–895

    PubMed  Google Scholar 

  • Spaak J, Montmerle S, Sundblad P, Linnarsson D (2005) Long-term bed rest-induced reductions in stroke volume during rest and exercise: cardiac dysfunction vs. volume depletion. J Appl Physiol 98(2):648–654

    PubMed  Google Scholar 

  • Srinivasan RS, Leonard JI, White RJ (1997) Mathematical modeling of physiological states. In: Nicogossian A, Mohler S, Gazenko O, Grigoriev A (eds) In: Space biology and medicine: humans in spaceflight, vol 3. vol book 2, American Institute of Aeronautics and Astronautics, Reston, pp 559–594

  • Sun D, Messina EJ, Kaley G, Koller A (1992) Characteristics and origin of myogenic response in isolated mesenteric arterioles. Am J Physiol 263(5 Pt 2):H1486–H1491

    PubMed  CAS  Google Scholar 

  • Sun B, Cao XS, Zhang LF, Liu C, Ni HY, Cheng JH, Wu XY (2003) Daily 4-h head-up tilt is effective in preventing muscle but not bone atrophy due to simulated microgravity. J Gravit Physiol 10(2):29–38

    PubMed  Google Scholar 

  • Sun B, Zhang LF, Gao F, Ma XW, Zhang ML, Liu J, Zhang LN, Ma J (2004) Daily short-period gravitation can prevent functional and structural changes in arteries of simulated microgravity rats. J Appl Physiol 97(3):1022–1031

    PubMed  Google Scholar 

  • Tanaka K, Gotoh TM, Awazu C, Morita H (2005) Regional difference of blood flow in anesthetized rats during reduced gravity induced by parabolic flight. J Appl Physiol 99(6):2144–2148

    PubMed  Google Scholar 

  • Tarasova O, Figourina I, Zotov A, Borovik A, Vinogradova O (2001) Effect of tail suspension on haemodynamics in intact and sympathectomized rats. Eur J Appl Physiol 85(5):397–404

    PubMed  CAS  Google Scholar 

  • Tarasova O, Kalentchuk V, Tsvirkoun D, Vinogradova O (2004) Effect of two-week tail suspension on forelimb and hindlimb [correction of hindlimd] small arteries in rats. J Gravit Physiol 11(2):P89–P90

    PubMed  CAS  Google Scholar 

  • Tedgui A, Mallat Z (2006) Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 86(2):515–581

    PubMed  CAS  Google Scholar 

  • Thijssen DH, Green DJ, Hopman MT (2011) Blood vessel remodeling and physical inactivity in humans. J Appl Physiol 111(6):1836–1845

    PubMed  Google Scholar 

  • Tuday EC, Meck JV, Nyhan D, Shoukas AA, Berkowitz DE (2007) Microgravity-induced changes in aortic stiffness and their role in orthostatic intolerance. J Appl Physiol 102(3):853–858

    PubMed  Google Scholar 

  • Tuday EC, Nyhan D, Shoukas AA, Berkowitz DE (2009) Simulated microgravity-induced aortic remodeling. J Appl Physiol 106(6):2002–2008

    PubMed  Google Scholar 

  • van den Akker J, Schoorl MJ, Bakker EN, Vanbavel E (2010) Small artery remodeling: current concepts and questions. J Vasc Res 47(3):183–202

    PubMed  Google Scholar 

  • Vaziri ND, Ding Y, Sangha DS, Purdy RE (2000) Upregulation of NOS by simulated microgravity, potential cause of orthostatic intolerance. J Appl Physiol 89(1):338–344

    PubMed  CAS  Google Scholar 

  • Verheyden B, Liu J, Beckers F, Aubert AE (2009) Adaptation of heart rate and blood pressure to short and long duration space missions. Respir Physiol Neurobiol 169(Suppl 1):S13–S16

    PubMed  Google Scholar 

  • Verheyden B, Liu J, Beckers F, Aubert AE (2010) Operational point of neural cardiovascular regulation in humans up to 6 months in space. J Appl Physiol 108(3):646–654

    PubMed  CAS  Google Scholar 

  • Vernikos J (1997) Artificial gravity intermittent centrifugation as a space flight countermeasure. J Gravit Physiol 4(2):P13–P16

    PubMed  CAS  Google Scholar 

  • Vernikos J, Ludwig DA, Ertl AC, Wade CE, Keil L, O’Hara D (1996) Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight. Aviat Space Environ Med 67(11):1069–1079

    PubMed  CAS  Google Scholar 

  • Vil-Viliams IF, Kotovskaya AR, Shipov AA (1997) Biomedical aspects of artificial gravity. J Gravit Physiol 4(2):P27–P28

    PubMed  CAS  Google Scholar 

  • Vil-Viliams IF, Kotovskaya AR, Nikolashin GF, Lukjanuk VJ (2001) Modern view on the short-arm centrifuge as a potential generator of artificial gravity in piloted missions. J Gravit Physiol 8(1):P145–P146

    PubMed  CAS  Google Scholar 

  • Watenpaugh DE, Hargens AR (1996) The cardiovascular system in microgravity. In: Handbook of physiology: environmental physiology, vol I. Am Physiol Soc, New York, pp 631–674

  • Waters WW, Ziegler MG, Meck JV (2002) Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance. J Appl Physiol 92(2):586–594

    PubMed  Google Scholar 

  • Watkins S, Barr Y (2010) Papilledema Summit: summary report NASA/TM-2010-216114

  • Webber CL Jr, Zbilut JP (1994) Dynamical assessment of physiological systems and states using recurrence plot strategies. J Appl Physiol 76(2):965–973

    PubMed  Google Scholar 

  • Wiener J, Loud AV, Giacomelli F, Anversa P (1977) Morphometric analysis of hypertension-induced hypertrophy of rat thoracic aorta. Am J Pathol 88(3):619–634

    PubMed  CAS  Google Scholar 

  • Wilkerson MK, Muller-Delp J, Colleran PN, Delp MD (1999) Effects of hindlimb unloading on rat cerebral, splenic, and mesenteric resistance artery morphology. J Appl Physiol 87(6):2115–2121

    PubMed  CAS  Google Scholar 

  • Wilkerson MK, Colleran PN, Delp MD (2002) Acute and chronic head-down tail suspension diminishes cerebral perfusion in rats. Am J Physiol Heart Circ Physiol 282(1):H328–H334

    PubMed  CAS  Google Scholar 

  • Wilkerson MK, Lesniewski LA, Golding EM, Bryan RM Jr, Amin A, Wilson E, Delp MD (2005) Simulated microgravity enhances cerebral artery vasoconstriction and vascular resistance through endothelial nitric oxide mechanism. Am J Physiol Heart Circ Physiol 288(4):H1652–H1661

    PubMed  CAS  Google Scholar 

  • Wilson TE, Shibasaki M, Cui J, Levine BD, Crandall CG (2003) Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans. J Appl Physiol 94(6):2113–2118

    PubMed  CAS  Google Scholar 

  • Woodman CR, Sebastian LA, Tipton CM (1995) Influence of simulated microgravity on cardiac output and blood flow distribution during exercise. J Appl Physiol 79(5):1762–1768

    PubMed  CAS  Google Scholar 

  • Woodman CR, Schrage WG, Rush JW, Ray CA, Price EM, Hasser EM, Laughlin MH (2001) Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius. J Appl Physiol 91(3):1091–1098

    PubMed  CAS  Google Scholar 

  • Xiao X, Grenon SM, Kim C, Sheynberg N, Hurwitz S, Williams GH, Cohen RJ (2005) Bed rest effects on human calf hemodynamics and orthostatic intolerance: a model-based analysis. Aviat Space Environ Med 76(11):1037–1045

    PubMed  Google Scholar 

  • Xie MJ, Zhang LF, Ma J, Cheng HW (2005a) Enhanced BK(Ca) single-channel activities in cerebrovascular smooth muscle cells of simulated microgravity rats. Acta Physiologica Sinica 57(4):439–445

    PubMed  CAS  Google Scholar 

  • Xie MJ, Zhang LF, Ma J, Cheng HW (2005b) Functional alterations in cerebrovascular K(+) and Ca(2 +) channels are comparable between simulated microgravity rat and SHR. Am J Physiol Heart Circ Physiol 289(3):H1265–H1276

    PubMed  CAS  Google Scholar 

  • Xie MJ, Ma YG, Gao F, Bai YG, Cheng JH, Chang YM, Yu ZB, Ma J (2010) Activation of BKCa channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats. Am J Physiol Cell Physiol 298(6):C1489–C1500

    PubMed  CAS  Google Scholar 

  • Xue JH, Zhang LF, Ma J, Xie MJ (2007) Differential regulation of L-type Ca2 + channels in cerebral and mesenteric arteries after simulated microgravity in rats and its intervention by standing. Am J Physiol Heart Circ Physiol 293(1):H691–H701

    PubMed  CAS  Google Scholar 

  • Xue JH, Chen LH, Zhao HZ, Pu YD, Feng HZ, Ma YG, Ma J, Chang YM, Zhang ZM, Xie MJ (2011) Differential regulation and recovery of intracellular Ca2 + in cerebral and small mesenteric arterial smooth muscle cells of simulated microgravity rat. PLoS ONE 6(5):e19775. doi:10.1371/journal.pone.0019775

    PubMed  CAS  Google Scholar 

  • Young LR, Paloski WH (2007) Short radius intermittent centrifugation as a countermeasure to bed-rest and 0-G deconditioning: IMAG pilot study summary and recommendations for research. J Gravit Physiol 14(1):P31–P33

    PubMed  Google Scholar 

  • Young L, Yajima K, Paloski W (2009) Artificial gravity research to enable human space exploration. International Academy of Astronautics, Paris

    Google Scholar 

  • Zhang LF (1994) Experimental studies on effects of simulated weightlessness on myocardial function and structure. J Gravit Physiol 1(1):P133–P136

    PubMed  CAS  Google Scholar 

  • Zhang LF (2001) Vascular adaptation to microgravity: what have we learned? J Appl Physiol 91(6):2415–2430

    PubMed  CAS  Google Scholar 

  • Zhang LF (2004) Vascular adaptation to microgravity. J Appl Physiol 97 (4):1584–1585; author reply 1585–1587

    Google Scholar 

  • Zhang LF (2005) System specificity in responsiveness to intermittent −Gx gravitation during simulated microgravity in rats. J Gravit Physiol 12:P1–P4

    Google Scholar 

  • Zhang LF, Bao JX (2005) Vascular adaptation to microgravity: role and implications of vascular local renin-angiotensin system. In: Hargens A, Takeda N, Singal P (eds) Adaptation biology and medicine, vol 4. Narosa, New Delhi, pp 329–339

    Google Scholar 

  • Zhang LF, Yu ZB, Ma J, Mao QW (2001a) Peripheral effector mechanism hypothesis of postflight cardiovascular dysfunction. Aviat Space Environ Med 72(6):567–575

    PubMed  CAS  Google Scholar 

  • Zhang LN, Zhang LF, Ma J (2001b) Simulated microgravity enhances vasoconstrictor responsiveness of rat basilar artery. J Appl Physiol 90(6):2296–2305

    PubMed  CAS  Google Scholar 

  • Zhang LF, Zhang LN, Meng QJ, Fu ZJ (2002) Research in differential adaptations of vessels to microgravity. J Gravit Physiol 9(1):P55–P58

    PubMed  Google Scholar 

  • Zhang LF, Sun B, Cao XS, Liu C, Yu ZB, Zhang LN, Cheng JH, Wu YH, Wu XY (2003) Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity. J Appl Physiol 95(1):207–218

    PubMed  Google Scholar 

  • Zhang LF, Cheng JH, Liu X, Wang S, Liu Y, Lu HB, Ma J (2008a) Cardiovascular changes of conscious rats after simulated microgravity with and without daily -Gx gravitation. J Appl Physiol 105(4):1134–1145

    PubMed  Google Scholar 

  • Zhang R, Jia G, Bao J, Zhang Y, Bai Y, Lin L, Tang H, Ma J (2008b) Increased vascular cell adhesion molecule-1 was associated with impaired endothelium-dependent relaxation of cerebral and carotid arteries in simulated microgravity rats. J Physiol Sci 58(1):67–73

    PubMed  CAS  Google Scholar 

  • Zhang R, Bai YG, Lin LJ, Bao JX, Zhang YY, Tang H, Cheng JH, Jia GL, Ren XL, Ma J (2009) Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats. J Appl Physiol 106(1):251–258

    PubMed  Google Scholar 

  • Zuj KA, Arbeille P, Shoemaker JK, Blaber AP, Greaves DK, Xu D, Hughson RL (2012) Impaired cerebrovascular autoregulation and reduced CO2 reactivity after long duration spaceflight. Am J Physiol Heart Circ Physiol 302(12):H2592–H2598

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I thank my co-workers MA Jin, MAO Qin-Wen, WANG Shou-Yan, Lu Hong-Bing, BAO Jun-Xiang, XIE Man-Jiang, XUE Jun-Hui, SUN Biao, GAO Fang, CHENG Jiu-Hua, LIU Yang, LIU Xin, LIN Le-Jian, and BAI Yun-Gang for their contributions. I also thank CHENG Jiu-Hua and SHENG Juan–Juan, who helped me to prepare the Figures, Tables, and Reference List. I am particularly grateful to Dr. A.R. Hargens for helpful discussions. This study was supported by the National Natural Science Foundation of China (Grant Nos. 30171032, 30470649, 30570677, and 31070839) and the Defense Medical Fund (Grant No. 01Q114).

Author information

Authors and Affiliations

  1. Department of Aerospace Physiology, Fourth Military Medical University, Xi’an, 710032, China

    Li-Fan Zhang

Authors
  1. Li-Fan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Li-Fan Zhang.

Additional information

Communicated by Nigel A.S. Taylor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, LF. Region-specific vascular remodeling and its prevention by artificial gravity in weightless environment. Eur J Appl Physiol 113, 2873–2895 (2013). https://doi.org/10.1007/s00421-013-2597-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-013-2597-8

Keywords

Search

Navigation