Mueller Patrick J, Sullivan Margaret J, Grindstaff Regina R, Cunningham J Thomas, Hasser Eileen M
Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri 65211-3300, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Jul;291(1):R46-52. doi: 10.1152/ajpregu.00622.2005.
Cardiovascular deconditioning occurs in astronauts after spaceflight or in individuals subjected to bed rest. It is characterized by an increased incidence of orthostatic intolerance. The mechanisms responsible for orthostatic intolerance are likely multifactorial and may include hypovolemia, autonomic dysfunction, and vascular and cardiac alterations. The arterial baroreflex is an important compensatory mechanism in the response to an orthostatic stress. In a previous study, we demonstrated that arterial baroreflex mediated sympathoexcitation was blunted in hindlimb-unloaded (HU) rats, a model of cardiovascular deconditioning. The arterial baroreflex also contributes to the regulation of vasoactive hormones including vasopressin and angiotensin II. In the present study, we tested the hypothesis that the neurohumoral response to hypotension is also attenuated in rats after 14 days of hindlimb unloading. To test this hypothesis, the vasodilator diazoxide (15 or 25 mg/kg) or saline (0.9%) was administered to produce hypotension or control conditions, respectively, in conscious HU and control rats. Plasma samples were collected and assayed for vasopressin and plasma renin activity (PRA). Diazoxide (25 mg/kg) produced significant increases in vasopressin and PRA compared with saline controls. HU rats exhibited significantly higher levels of vasopressin at rest and the increase in vasopressin levels during hypotension was enhanced by hindlimb unloading. Neither resting nor hypotension-induced PRA was altered by hindlimb unloading. These data suggest that although baroreflex-mediated sympathoexcitation is blunted by hindlimb unloading, hypotension-induced vasopressin release is enhanced and hypotension-induced PRA is unaffected. Increased circulating vasopressin may serve to compensate for blunted baroreflex regulation of sympathetic nervous activity produced by hindlimb unloading or may actually contribute to it.
心血管功能失调发生在航天后的宇航员或接受卧床休息的个体身上。其特征是体位性不耐受的发生率增加。导致体位性不耐受的机制可能是多因素的，可能包括血容量减少、自主神经功能障碍以及血管和心脏改变。动脉压力反射是对体位性应激反应中的一种重要代偿机制。在先前的一项研究中，我们证明在心血管功能失调模型后肢去负荷（HU）大鼠中，动脉压力反射介导的交感神经兴奋减弱。动脉压力反射也有助于调节包括血管加压素和血管紧张素II在内的血管活性激素。在本研究中，我们测试了这样一个假设，即后肢去负荷14天的大鼠对低血压的神经体液反应也会减弱。为了验证这一假设，分别给清醒的HU大鼠和对照大鼠注射血管扩张剂二氮嗪（15或25mg/kg）或生理盐水（0.9%）以产生低血压或对照状态。采集血浆样本并检测血管加压素和血浆肾素活性（PRA）。与生理盐水对照组相比，二氮嗪（25mg/kg）使血管加压素和PRA显著增加。HU大鼠在静息时血管加压素水平显著更高，后肢去负荷增强了低血压期间血管加压素水平的升高。后肢去负荷既未改变静息时的PRA，也未改变低血压诱导的PRA。这些数据表明，尽管后肢去负荷使压力反射介导的交感神经兴奋减弱，但低血压诱导的血管加压素释放增强，而低血压诱导的PRA未受影响。循环血管加压素增加可能有助于代偿后肢去负荷导致的压力反射对交感神经活动调节的减弱，或者实际上可能促成了这种减弱。
