We propose to continue studies of kidney function utilizing micropuncture and microperfusion techniques to measure glomerula and tubular function, and multiunit and single unit nerve recordings for assessment of neural control of renal function. Parallel studies in young genetically hypertensive rats of the Okamoto-Aoki strain (SHR) and appropriate controls will provide insight into the role of renal function and its regulation by neurohumoral mechanisms in the development of hypertension in this model, which resembles essential hypertension in humans. Inhibition of prostaglandin synthesis blunts the natriuretic response to denervation; the nephron sites of this apparently permissive action of prostaglandins will be identified in both acutely and chronically denervated kidneys. The role of prostaglandins in modulating the antinatriuretic response to renal nerve stimulation will also be investigated, and the question whether altered basal nerve activity and/or impaired prostaglandin synthesis is responsible for the absence of denervation natriuresis in certain strains of rats and after certain forms of anesthesia will be addressed. The relative frequency of occurence of various types of renal chemoreceptors and mechanoreceptors, and their responsiveness to physiologic stimuli, will be measured in young SHR and normotensive controls. The activity of single efferent renal nerve fibers will also be measured, and their reflex responsiveness to the activation of chemoreceptors of the R1 and R2 subtypes and of somatic afferents in the radial nerve will be assessed. The role of tubular glomerular feedback (TGF) in the autoregulation of glomerular ultrafiltration and renal blood flow will be investigated in normotensive and genetically hypertensive rats. Studies are specifically designed to gain insight into mechanisms responsible for, and functional consequences of, enhanced TGF activity in young genetically hypertensive rats. Mechanisms responsible for continued autoregulation when TGF is impaired will be investigated, and the effects of synthetic atrial natriuretic factor on glomerular ultrafiltration dynamics, segmental vascular resistance, and TGF will be examined.
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