Neural Mechanisms in Cariorenal Regulation

心血管调节的神经机制

• 批准号: 7596574
• 负责人: THOMAS E LOHMEIER
• 金额: $ 32.39万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-15 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596574
• 关键词: Adrenergic Agents; Attenuated; Baroreflex; Cardiac; Cardiovascular system; Excretory function; Hypertension; Hypotension; Kidney; Mediating; Pattern; Peripheral; Pressoreceptors; Regulation; Time; adrenergic; neuromechanism

The sympathetic nervous system plays an important role in the pathogenesis of hypertension, yet the precise determinants of sympathetic activation are unresolved. Furthermore, the efferent mechanisms that account for long-term sympathetically-induced alterations in arterial pressure are unclear. In this regard, there is considerable controversy as to whether alterations in renal excretory function are of paramount importance in mediating the chronic effects of the nervous system on arterial pressure. In short, progress in understanding the above issues has been limited by the lack of clinical and experimental methods for critically studying sympathetic function in the chronic regulation of arterial pressure. Because of the crucial role of the baroreflex in acute regulation of arterial pressure, there has been a long-standing interest in the possibility that baroreflexes might chronically influence the level of sympathetic activity and arterial pressure in hypertension. The potential importance of such a relationship has been highlighted by clinical observations demonstrating that the sympathetic arm of the baroreflex is impaired in primary hypertension. However, because the baroreflex resets in the direction of the ambient pressure, a role for the baroreflex in long-term pressure control is often discounted. On the other hand, because of technical limitations, it is important to emphasize that there is little empirical evidence from chronic studies that supports the notion that baroreflex resetting is complete in hypertension. In fact, recent innovative studies in animals with experimentally-induced hypertension suggest that the baroreflex does not totally reset and has sustained sympathoinhibitory effects in hypertension. These studies further indicate baroreflex activation chronically suppresses renal sympathetic nerve activity and promotes sodium excretion, responses expected to attenuate the severity of hypertension. The relevance of these studies to clinical hypertension, however, is limited by their relatively short duration (most commonly one week). In the proposed studies, we will use a novel approach to evaluate several aspects of baroreflex function over at least 3 weeks of controlled baroreflex activation. We will use a combination of sophisticated techniques in chronically instrumented dogs to determine whether the central nervous system contributes to chronic resetting of the baroreflex and whether chronic activation of the baroreflex does indeed have sustained effects to inhibit renal sympathetic nerve activity and promote sodium excretion. To achieve these goals, the carotid baroreflex will be chronically activated by electrical stimulation of the carotid sinuses. Chronic electrical activation of the carotid baroreflex leads to sustained suppression of sympathetic activity and arterial pressure and is an ideal technique for determining the importance of central resetting in attenuating the sympathoinhibition induced by increased baroreceptor activity because it allows for precise control of central afferent input patterns. Additionally, in combination with other measures, this methodology permits direct evaluation of the chronic effects of baroreflex activation on renal sympathetic outflow and excretory function. Isotope dilution methodology will be used in these studies to determine whole body and renal norepinephrine spillover to plasma as indices of central and renal specific sympathetic outflow. These studies will provide unique insight into the chronic functional effects of the baroreflex in hypertension and the importance of the kidneys in mediating long-term changes in-arterial pressure during alterations in central sympathetic outflow.

交感神经系统在高血压的发病机制中起着重要作用，但其发病机制尚不明确