Hasser E M, Moffitt J A
Dalton Cardiovascular Research Center, Department of Veterinary Biomedical Sciences, University of Missouri, Columbia, Missouri 65211, USA.
Ann N Y Acad Sci. 2001 Jun;940:454-68. doi: 10.1111/j.1749-6632.2001.tb03698.x.
Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently arises from sources other than the caudal ventrolateral medulla. If similar alterations in control of the sympathetic nervous system occur in humans in response to cardiovascular deconditioning, it is likely that they play an important role in the observed tendency for orthostatic intolerance. Combined with potential changes in vascular function, cardiac function, and hypovolemia, the predisposition for orthostatic intolerance following cardiovascular deconditioning would be markedly enhanced by blunted ability to reflexly activate the sympathetic nervous system.
长时间卧床休息或处于微重力环境下的人会出现心血管系统失健，其特征为静息性心动过速、运动能力下降以及易于出现体位性不耐受。心血管功能的这些变化可能是多种因素共同作用的结果，包括体液平衡控制的改变或心脏改变导致心输出量维持不足、动脉或静脉血管功能改变、心血管激素激活减少以及自主神经反射功能减弱。有证据表明这些机制各自都发挥了作用。交感神经系统反射激活减弱及随后的血管收缩似乎起着重要作用。利用后肢去负荷（HU）大鼠这一失健动物模型开展的研究，评估了动脉压力反射对交感神经系统控制改变的潜在作用。这些研究表明，HU会导致压力反射介导的肾和腰交感神经活动在对低血压刺激作出反应时激活减弱。HU大鼠在出血期间维持动脉血压的能力较差，这表明增加交感神经活动的能力减弱对动物具有功能影响。HU后血管加压素分泌的反射控制似乎增强。压力反射介导的交感神经兴奋减弱似乎涉及中枢神经系统功能改变。HU大鼠对动脉压变化作出反应时的压力感受器传入活动未改变。然而，HU后，对于给定的传入输入减少，传出交感神经活动的增加减弱。压力感受器输入的这种中枢神经系统处理改变似乎涉及延髓头端腹外侧（RVLM）的作用。具体而言，似乎HU后GABAA介导的对RVLM的紧张性抑制增强。增强的抑制显然源于尾端腹外侧延髓以外的来源。如果人类因心血管失健而出现类似的交感神经系统控制改变，那么它们很可能在观察到的体位性不耐受倾向中起重要作用。与血管功能、心脏功能和血容量不足的潜在变化相结合，心血管失健后体位性不耐受的易感性会因反射性激活交感神经系统的能力减弱而显著增强。
