THE NEURAL CONTROL OF RENAL FUNCTION

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The overall objective of the proposed research is to test the hypothesis that the renal nerves represent an important afferent and efferent control system for the regulation of several renal functions in normal and pathological conditions. The specific aims are: (1) evaluate efferent renal sympathetic nerve activity (ERSNA) as a trophic influence on renal sensory receptor in the rat, (2/3) assess renorenal reflexes and their neural connections in the cat, (4) localize the modulating effect of dietary sodium intake on the left atrial cardiopulmonary baroreceptor ERSNA reflex in the rat, (5) measure the effect of dietary sodium intake on the ERSNA response to selective unloading of left atrial cardiopulmonary baroreceptors in the conscious rat, (6) measure the time course of ERSNA in response to changes in dietary sodium intake in the conscious rat, (7) determine the functional role of renal alpha-2 adrenoceptors in the rat, (8) measure the contribution of ERSNA to the renal sodium retention of nephrotic syndrome in the conscious rat, (9/10) assess the role of activation of hepatic mechanoreceptors producing increased ERSNA and renal sodium retention in hepatic cirrhosis with ascites in the conscious dog. Renal blood flow will be measured with an electromagnetic flow probe/meter and glomerular filtration rate will be measured by the urinary clearance of insulin. Standard electrophysiologic techniques will be used for the measurement of renal nerve activity in anesthetized animals and, with previously validated technical modifications, in conscious animals devoid of the confounding influence of anesthesia and/or surgical trauma. The possibility that ERSNA constitutes an important efferent mechanism for the avid renal sodium retention characteristic of the human disease states, nephrotic syndrome and hepatic cirrhosis with ascites, will be examined in the established experimental animal models, adriamycin nephropathy in the rat and primary biliary cirrhosis from common bile duct ligation in the dog, respectively. Therefore, these studies will serve to more clearly define the role of the renal innervation in the control of renal function in both health and disease.