The continuing goal of this ongoing project is the further delineation of the factors and mechanisms contributing to the regulation of the process of glomerular filtration and tubular reabsorption, primarily in the proximal convoluted tubule. Utilizing micropuncture techniques in the Munich-Wistar rat we can measure directly the nephron filtration rate and all the pressures, flows and permeabilities that constitute the determinants of glomerular ultrafiltration and the factors that affect uptake of fluid reabsorption from the proximal tubule. We have observed that the glomerular permeability coefficient (LpA) is reduced and influences the nephron filtration rate in such conditions as chronic NaCl depletion, increased ureteral pressure and in the kidney exposed to hypertension (Goldblatt) and studies will determine if this decrease in LpA is mediated by the action of the renal hormone, angiotensin II. Other studies will examine the effects of alpha adrenergic agonists and intense renal sympathetic nerve stimulation upon the nephron filtration rate and the determinants of ultrafiltration. In parallel studies using micropuncture and in vivo microperfusion techniques in the rat and analysis of AII hormonal receptors on dissected proximal tubules from the rabbit, we will further delineate the role of AII in influencing the rate of reabsorption in the proximal convoluted tubule. Similar micropuncture techniques will delineate the specific mechanisms whereby intense renal sympathetic nerve stimulation may effect proximal tubule reabsorption. Continuing studies will also further delineate mechanisms which link the rate of proximal tubular reabsorption to the rate of nephron filtration and quantitate the relative contributions of intraluminal flow dependency of reabsorption and extraluminal """"""""physical factors"""""""" in glomerulo-tubular balance. Studies are also designed to examine the determinants of glomerular ultrafiltration and proximal tubular reabsorption in response to large changes in systemic blood pressure in normal rats and rats in which tubuloglomerular feedback activity has been suppressed or eliminated. These studies in the aggregate will evaluate factors which significantly contribute to the regulation of glomerular filtration rate and proximal tubular reabsorption, important factors in the maintenance of volume homeostasis.
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