RENAL NERVES AND CENTRAL MONOAMINES IN HYPERTENSION

高血压中的肾神经和中枢单胺

• 批准号: 3449463
• 负责人: RICHARD H ALPER
• 金额: $ 5.08万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3449463
• 关键词: afferent nerve; brain stem; denervation; dopamine; hypothalamus; kidney circulation; nerve; neurochemistry; neurotransmitters; norepinephrine; renal artery obstruction; serotonin; vascular resistance

The role of afferent renal nerves in cardiovascular regulation is controversial. Despite a large body of data, there is little agreement on cardiovascular consequences of afferent renal nerve stimulation. Studies do suggest, however, that renovascular hypertension is reversed by renal denervation, as a reflex decrease in efferent sympathetic tone and arterial pressure. This may be mediated by hypothalamic norepinephrine. To date there is little experimental evidence relating afferent renal nerve activity to central monoamine metabolism, although circumstantial evidence does exist. In conscious rats, renal stenosis (RSt) following sino-aortic deafferentation and captopril, and the intrarenal infusion of bradykinin increase arterial pressure and sympathetic nerve activity. These effects are abolished by prior denervation of the kidney. The two models will permit studies on functional roles of central monoamines in afferent renal nerve-dependent cardiovascular responses in conscious rats. This project will attempt to provide significant new information on the ability of monoamines in specific brain regions to alter various cardiovascular parameters. The first studies will describe effects of renal denervation and deafferentation on the synthesis and metabolism of hypothalamic and brainstem monoamines. A second series of studies will describe the effects of RSt and intrarenal bradykinin on central biogenic amine dynamics. These experiments are intended to provide information on specific central sites and neurotransmitters that mediate cardiovascular responses to afferent renal nerve-dependent stimuli. The final studies will use data from the initial experiments and explore their functional importance. This is accomplished by making specific, local interruptions in neurotransmitter pathways implicated by the neurochemical studies. Following local central injections of lidocaine, specific receptor agonists, antagonists, and neurotoxins, or discrete electrolytic lesions, cardiovascular responses to RSt and/or intrarenal bradykinin will be observed. In this manner a systematic description of sites and neurotransmitters involved in centrally-mediated afferent renal nerve reflexes and cardiovascular physiology will evolve. This will provide insight into central, cardiovascular and neural mechanisms in the pathogenesis of hypertension

传入肾神经在心血管调节中的作用是