Neural Mechanisms in Cardiorenal Regulation

心肾调节的神经机制

• 批准号: 6781625
• 负责人: THOMAS E LOHMEIER
• 金额: $ 19.02万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6781625
• 关键词: angiotensin /renin /aldosterone hypertension; angiotensin II; baroreceptors; baroreflex; blood pressure; blood volume; cardiovascular function; clinical research; denervation; dietary sodium; dogs; electrolyte balance; electrostimulus; neuroendocrine system; neuroregulation; norepinephrine; nutrition related tag; obesity; renin angiotensin system; salt intake; saluresis; sympathetic nervous system

The sympathetic nervous system plays an important role in the pathogenesis of hypertension, although the precise mechanisms are unclear. This is because techniques are needed to critically evaluate the role of the nervous system in the chronic regulation of arterial pressure. There has been considerable interest in the impact of baroreflexes on sympathetic activity and arterial pressure in chronic hypertension, particularly since baroreflex dysfunction is commonly associated with hypertension. As baroreflexes reset in the direction of the prevailing level of pressure, it has been argued that they cannot possibly play a role in long-term regulation of arterial pressure. However, novel approaches in chronically instrumented animals have recently shown that baroreflexes do not totally reset in hypertension and that they promote sodium excretion by producing sustained reductions in renal sympathetic nerve activity (RSNA). These findings suggest that baroreflex mediated inhibition of RSNA may play an important compensatory role in hypertensxon. The proposed studies will evaluate this concept by employing 2 techniques: 1) prolonged activation of the baroreflex by bilateral electrical stimulation of the carotid sinus, and 2) abrogation of the baroreflex by sinoaortic denervation (SAD). As carotid baroreceptor afferent input into the CNS will be constant during carotid sinus stimulation, this will permit several novel determinations including: 1) the long-term hypotensive response to prolonged baroreflex activation in normal dogs and the role of the renal nerves in mediating the hypotension, and 2) the long-term hypotensive response to baroreflex activation in hypertensive dogs and the importance of a responsive renin-angiotensin system in mediating the hypotension. The compensatory role of the baroreflex in attenuating different models of hypertension will be tested further by SAD. We hypothesize that sustained baroreflex activation can attenuate the severity of hypertension by chronically suppressing RSNA. Further, we propose that suppression of renin secretion contributes to the hypotensive effects of baroreflex mediated renal sympathoinhibition. Thus, we expect the hypotensive response to baroreflex activation to be attenuated in hypertension produced by infusion of either angiotensin or aldosterone, but not in obesity hypertension in which increased renin secretion is linked to increased RSNA. Insight from these studies will be directly relevant to neurally mediated renal compensations in hypertension.

交感神经系统在高血压的发病机制中起着重要作用，但其确切机制尚不清楚。这是因为需要技术来批判性地评估神经系统在动脉压慢性调节中的作用。压力感受器反射对慢性高血压患者交感神经活动和动脉压的影响已经引起了相当大的兴趣，特别是因为压力感受器反射功能障碍通常与高血压有关。随着压力反射朝着当前压力水平的方向重置，有人认为它们不可能在长期调节压力的过程中发挥作用。 动脉压。然而，最近在慢性仪器化动物身上的新方法表明，压力反射在高血压患者中并不完全恢复，它们通过产生肾脏交感神经活动(RSNA)的持续减少来促进钠的排泄。这些结果提示，压力感受性反射对RSNA的抑制可能在高血压中起着重要的代偿作用。拟议的研究将使用两种技术来评估这一概念：1)双侧电刺激延长压力感受器反射的激活 刺激颈动脉窦，2)去窦弓神经(SAD)消除压力感受性反射。由于颈动脉压力感受器传入中枢神经系统的传入在刺激颈动脉窦期间是恒定的，这将允许一些新的测定，包括：1)正常狗对长时间压力反射激活的长期低血压反应和肾神经在调节低血压中的作用；2)高血压狗对压力反射激活的长期低血压反应和反应性肾素-血管紧张素系统在调节低血压中的重要性。压力反射在减弱不同高血压模型中的代偿作用将通过SAD进一步检验。我们假设持续的压力感受器反射 激活可以通过慢性抑制RSNA来减轻高血压的严重程度。此外，我们认为肾素分泌的抑制参与了压力感受性反射介导的肾交感神经抑制的降压作用。因此，我们预计压力感受器反射激活的降压反应在血管紧张素或醛固酮输注引起的高血压中减弱，但在肥胖性高血压中不会减弱，在肥胖性高血压中肾素分泌增加与RSNA增加有关。这些研究的洞察力将与高血压患者的神经介导的肾代偿直接相关。