Studies are proposed to define the role of vasopressin (AVP) in the normal regulation of renal medullary blood flow. We hypothesize that the actions of AVP on the medullary circulation provide a vital link to optimize the ability of the kidney to retain or lose body fluids. Preliminary studies indicate that AVP secretion has a profound influence on the pressure- diuresis.natriuresis relationship whereby in times of volume expansion medullary flow is increased by reduction of AVP with the opposite occurring in times of fluid retention.
Three specific aims and 9 protocols are proposed in rats: 1) determine the effects of small physiological changes of plasma AVP on medullary blood flow and associated changes of the pressure-diuresis-natriuresis relationships in decerebrate rats and unanesthetized rats using implanted optical fiber and laser-Doppler flowmetry; 2) functionally localize medullary vascular sites where AVP modulates blood flow using micropuncture techniques; and localize vascular VI and V2 receptors in microdissected vessels from the cortical and medullary circulation using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting techniques; and 3) evaluate the consequences of these mechanisms in the long-term control of arterial pressure and determine why chronic administration of a specific VI agonist causes sustained hypertension while administration of AVP does not. The role of V2 receptor stimulation via nitric oxide (NO), bradykinin, and prostaglandins in opposing the hypertensive effects of AVP will be examined. The studies will utilize techniques ranging from chronically instrumented, unanesthetized rats to molecular biology.
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