This is a proposal to continue characterizing the mechanisms of regulation and areas of functional responsibility of the renal kallikrein-kinin and prostaglandin systems, interacting hormonal systems which contribute to the regulation of renal function and blood pressure. We propose experimentation in the following areas. Area 1: Investigation of the Mechanisms and Physiological Significance of the Regulatory Influence of Kinins on Renal Function. Experiments will be conducted in perfused kidneys and isolated glomeruli and tubules (a) to characterize the renal actions of kinins in terms of receptors involved and relationship to cGMF and prostaglandin synthesis (b) to investigate the effects of purified kininogen on renal function and intrarenal generation of kinins. Prostaglandins and cGMP; and (c) to assess the renal functional response to treatment with kinin receptor antagonists with excess vasopressin or high protein intake, which conditions are known to increase renal kinins. Area 2: Investigation of the Contribution of Kinins to the Blood Pressure Lowering Effect of Renal Artery Unclipping in Renal Hypertension. Experiments will be conducted (a) to investigate relationships between the hypotensive response to renal artery unclipping and changes in plasma levels and renal secretion of Kinins, and (b) assess the effect of Kinin receptor antagonists on the hypotensive response to unclipping. Area 3: Investigation of the Relationship Between Kinins, Prostaglandin Synthesis and Trizlvceride Metabolism in Renal Medullary Cells. Experiments will be conducted in cultured rabbit renomedullary interstitial cells (a) to characterize the triglyceride lipase of RMIC and study its regulation by kinins, cAMP-mediated renal 1 hormones and osmolality; and (b) to examine the effects of kinins and other hormone that stimulate triglyceride lipase activity on eicosanoid synthesis by renomedullary interstitial cells.
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