The primary long term objective of this proposed project is the elucidation of the physiological mechanisms regulating renal hemodynamics and renal autoregulatory behavior at the whole kidney level as well as in single nephrons. Emphasis will be focused on the intrinsic intrarenal regulatory mechanisms operating at the single nephron level that collectively lead to the regulation of renal blood flow and glomerular filtration rate. In this regard, continued effort will be directed at a comprehensive evaluation of the distal tubular glomerular feedback mechanism, and its role as a mediator of renal autoregulatory behavior. Most of the studies which are outlined in this proposal will utilize in vivo micropuncture and microperfusion techniques in anesthetized rats and dogs. The distal tubular glomerular feedback mechanism will be studied by measuring single nephron glomerular filtration rate or stop flow pressure during perfusion from the late proximal tubule site or retrograde perfusion from the early distal tubule site. The proposed studies will investigate further the following concepts and issues: a) the hypothesis that the distal tubular-glomerular feedback mechanism mediates renal autoregulatory responses, b) the hypothesis that the total solute concentration within the lumen and the early distal tubule is most closely associated with feedback mediated alterations in glomerular function, c) the individual sequence of events responsible for information transfer from the macula densa cells to the vascular contractile elements, with emphasis on the role of macula densa cell cytoplasmic calcium as a cellular messenger system, d) the specific contractile elements of the glomerulus most directly involved in feedback mediated alterations in glomerular function, e) the interaction of the predominant intrarenal hormone systems with the distal tubular-glomerular feedback mechanism, and f) the interaction of the contractile elements of the renal circulation with the intrarenal generation of angiotensin II.
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