The long term goals are to clarify the intrarenal mechanisms of blood flow and GFR regulation, and the interaction of these mechanisms with signals originating elsewhere in the body. Experiments will be conducted in 3 related areas. 1) The effect of acute hypertension on fluid and electrolyte transport in the proximal tubule and loop of Henle will be studied by in situ microperfusion to determine whether the loop of Henle responds to an increased fluid load delivered from the proximal tubule or directly to hypertension; to determine whether the proximal tubule response is triggered by intrarenal angiotensin II; and to determine whether the proximal tubule response involves modulation of Na-H exchange, NaCl transport, or both. A new method for measuring tubular flow rate will also be used to confirm that proximal tubule reabsorption is inhibited by hypertension. 2) Inter- and intracellular mechanisms involved in tubuloglomerular feedback (TGF) will be studied in Amphiuma means. The effect of changes in flow rate in the early distal tubule on transport of Cl across the epithelium will be measured, in combination with measurements of blood flow in afferent and efferent arterioles, to establish that there is a functional connection. Additional microelectrode measurements will be made in mesangial cells and in vascular smooth muscle cells of the afferent arteriole, to test hypotheses about the nature of the coupling. 3) Medullary blood flow rate will be measured in individual vasa recta to test the sensitivity to angiotensin II, to test an hypothesis about the interaction between angiotensin II and autoregulation, to determine whether prostaglandins modulate the action of angiotensin II on juxtamedullary efferent arterioles, and to test whether atrial natriuretic factor affects vasa recta flow independently on an effect on reabsorption from medullary collecting ducts.
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