Neural Mechanisms in Cardiorenal Regulation

心肾调节的神经机制

• 批准号: 7062942
• 负责人: THOMAS E LOHMEIER
• 金额: $ 19.77万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7062942
• 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中起着重要作用，但确切的机制尚不清楚。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。在慢性高血压中，压力反射对交感神经活动和动脉压的影响引起了相当大的兴趣，特别是因为压力反射功能障碍通常与高血压相关。由于压力感受性反射在当前压力水平的方向上重置，因此有人认为它们不可能在长期调节中发挥作用。 动脉压然而，新的方法在慢性仪器动物最近表明，压力反射不完全重置高血压，他们促进钠排泄产生持续减少肾交感神经活动（RSNA）。这些发现表明压力反射介导的RSNA抑制可能在高血压中发挥重要的代偿作用。拟议的研究将通过采用2种技术来评估这一概念：1）通过双侧电刺激延长压力感受器反射的激活 刺激颈动脉窦; 2）通过去窦弓神经（SAD）消除压力感受性反射。由于在颈动脉窦刺激期间，进入CNS的颈动脉压力感受器传入输入将是恒定的，这将允许几个新的确定，包括：1）正常犬对压力反射长时间激活的长时程降压反应及肾神经在介导低血压中的作用;和2）高血压犬对压力反射激活的长期过度反应以及反应性肾素-血管紧张素系统介导低血压。压力感受性反射对不同高血压模型的代偿作用将通过SAD进一步检验。我们假设持续的压力反射 激活可以通过长期抑制RSNA来减轻高血压的严重程度。此外，我们提出，抑制肾素分泌有助于压力感受性反射介导的肾交感神经抑制的扩张效应。因此，我们预计，压力感受性反射激活的过度反应，以减弱在高血压产生的血管紧张素或醛固酮的输液，但不是在肥胖高血压，其中增加的肾素分泌增加与RSNA增加。这些研究的结果将直接关系到高血压的神经介导的肾代偿。