The primary long term objectives of this project are to elucidate the physiological mechanisms responsible for renal autoregulatory behavior at both the whole kidney and single nephron level and to determine the role of intrarenally formed angiotensin II in the regulation of renal hemodynamics. Emphasis will be focused on the intrarenal regulatory mechanisms operating at the single nephron level that collectively regulate renal blood flow and glomerular filtration rate. Continued effort will be directed at a comprehensive evaluation of the distal tubular-glomerular feedback (TGF) mechanism, and its role as a mediator of renal autoregulatory behavior. Studies will utilize in vivo micropuncture and microperfusion techniques in anesthetized rats and dogs. We will also utilize more extensively our newly developed in vitro juxtamedullary blood perfused nephron preparation to study these problems in a more direct manner. The TGF mechanism will be studied by measuring single nephron glomerular filtration rate or glomerular pressure during perfusion from a late proximal tubular site or from an early distal tubular site. Studies evaluating the role of intrarenally generated angiotensin II will utilize peritubular capillary infusions or in vitro superfusion of angiotenin I. Using both in vivo and in vitro approaches, we will investigate further a) the relative contributions of the TGF mechanism and the myogenic mechanism to overall autoregulatory responses b) the regulatory influence of enhanced intrarenal formation of angiotensin II on afferent and efferent arteriolar resistances, the glomerular filtration coefficient and the sensitivity of the TGF mechanism, and c) the specific localization of the resistance adjustments during autoregulation. Further attention will be directed to the nature of the messenger systems responsible for the mediation of signals from the macula densa cells to the effector contractile components.
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