The overall objective of this proposal is to investigate the role of afferent renal nerves (ARN) in cardiovascular regulation and in the development of renal hypertension. Current evidence suggests that specialized populations of ARN with mechanoreceptive or chemoreceptive properties may influence renal excretory function through specific reno-renal reflexes and may alter peripheral sympathetic outflow. Moreover, a significant role for ARN in the established phase of experimental renal hypertension has been suggested. The precise nature of this role and the stimulus and time course for the expression of the ARN component remain unknown. It is also unclear whether ARN directly influence cardiovascular control mechanisms under physiological conditions. Recent work from this laboratory has described a sympathoexcitatory """"""""renal pressor (RP) reflex"""""""" produced by acute renal artery stenosis (RST) in conscious animals with reduced arterial baroreflex and renin-angiotensin (R-A) system responsiveness to minimize coactivation of these regulatory systems. The work proposed here will examine the hypothesis that the RP reflex also operates in animals with an intact R-A system and baroreflexes in the production of hypertension during RST and in the integrated response to hemorrhage. Chronic microinstrumentation techniques and Doppler flowmetry will be used to evaluate the influence of RST on peripheral hemodynamics, regional vascular resistance, and circulatory vasconstrictor hormones in conscious, unrestrained rats. Electrophysiological studies of ARN activation will be performed in conjunction with hemodynamic analysis, in decrebrate paralyzed rats. These techniques will be used to address the following specific aims: 1) to determine if chronic RST can produce sustained hypertension solely through activation of ARN, 2) to determine the influence of the contralateral kidney during activation of the RP reflex, 3) to identify the interaction between the RP reflex and R-A system, and 4) to clarify the intrarenal ARN stimulus produced by RST and the role of prostaglandins and other renal autocoids in the direct activation or modulation of ARN receptors.
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