SYMPATHETIC RENAL INTERACTIONS IN HYPERTENSION

高血压中的交感肾相互作用

基本信息

批准号：
3337697
负责人：
RICHARD E KATHOLI
金额：
$ 8.69万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-07-01 至 1986-11-30
项目状态：
已结题

项目摘要

This proposal will examine interactions involving the kidney, the renin-angiotensin-aldosterone system and the sympathetic nervous system by studying the role of the renal nerves in renovascular hypertension. Denervation of the clipped kidney in the one-kidney one-clip and the two-kidney one-clip rat with established hypertension results in a decrease in arterial pressure that is not explained by changes in renin or sodium excretion. This depressor effect of renal denervation is associated with decreased sympathetic nervous system activity. These findings led to the hypothesis that in response to clipping, the afferent renal nerves activate the sympathetic nervous system in the Goldblatt models of hypertension. To define the role of the renal nerves in the development of Goldblatt hypertension, the arterial pressure and sympathetic response to clipping will be compared in sham-operated and renal denervated animals chronically treated with converting enzyme inhibitor SQ 14225 (6 mg/kg/day) to prevent angiotensin II formation. Plasma norepinephrine and arterial pressure response to ganglionic blockade with 30 mg/kg hexamethonium bromide will be measured in conscious resting animals as indices of sympathetic nervous system activity. Recent studies by the investigator reveal that renal artery infusion of adenosine (0.85 plus or minus 0.08 Mug/kg/min) produces hypertension by activating the sympathetic nervous system when the renal nerves are intact in the conscious dog. This suggests that there may be adenosine sensitive nerve endings in the kidney which modulate sympathetic nervous system activity. To define the cardiac, contralateral renal efferent sympathetic and adrenal medullary responses to intrarenal adenosine, functional and neurophysiological studies will be performed before and after renal denervation in the chloralose anesthetized dog. Pilot studies reveal that intrarenal mineralocorticoid administration attenuates the hypertensive response to renal artery adenosine infusion in the conscious dog. To determine whether increased potassium and/or hydrogen ion excretion are involved in the mechanism by which mineralocorticoid treatmen blunts the intrarenal adenosine response, renal afferent nerve response to adenosine will be measured before and after increasing renal pelvic potassium and/or hydrogen ion concentrations in the anesthetized dog.

该建议将检查涉及肾脏的互动，肾素 - 血管紧张素 - 醛固酮系统和交感神经系统研究肾神经在肾血管高血压中的作用。在单封单张纸和具有已建立高血压的两型kidney单盘大鼠导致降低在动脉压中未通过肾素或钠的变化来解释的动脉压排泄。肾脏神经的这种抑制剂效应与交感神经系统活动减少。这些发现导致了假设在响应剪接时，传入的肾神经激活高血压戈德布拉特模型中的交感神经系统。到定义肾神经在Goldblatt发展中的作用高血压，动脉压和对剪辑的交感神经反应将在慢性化的假手术和肾脏剥离的动物中进行比较用转换酶抑制剂SQ 14225（6 mg/kg/天）处理以防止血管紧张素II的形成。血浆去甲肾上腺素和动脉压 30 mg/kg六甲基溴化物对神经节封锁的反应将是在有意识的休息动物中测量作为交感神经的指标系统活动。研究者的最新研究表明，肾动脉输注通过当肾神经完好无损时激活交感神经系统在有意识的狗中。这表明可能有腺苷敏感肾脏中的神经末端调节交感神经系统活动。定义心脏，对侧肾脏传出同情和肾上腺髓质对肾内腺苷，功能和神经生理研究将在肾脏前后进行氯化狗麻醉狗的神经。试点研究表明肾内皮质激素给药可减轻高血压对有意识狗的肾动脉输注的反应。到确定钾和/或氢离子排泄是否增加是涉及矿物皮质型治疗的机制肾内腺苷反应，肾传入神经对腺苷的反应将在增加肾骨盆钾和/或增加肾脏骨盆钾之前和之后进行测量麻醉犬中的氢离子浓度。