REGULATION OF INTRARENAL DOPAMINE AVAILABILITY

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This 12 month period will consist of two 6 month visits; the first will be from Jan. 1, 1998 - June 30, 1998 and the second will be from Nov. 1, 1998 or Dec. 1, 1998 to April 30, 1999 or May 31, 1999. The overall goal is to define the cellular and molecular mechanisms of the regulation of renal tubular sodium transport by norepinephrine (NE) and dopamine (DA). This has health implications for the pathogenesis of hypertension, viewed as resulting from diminished renal sodium excretory capacity due to decreased intrarenal availability and/or action of DA. In this project, the effect of inhibition of DA metabolism on the intrarenal availability and/or action of DA will be examined in normotensive and hypertensive rats. Effects on whole kidney sodium handling will be correlated with effects on activity of renal tubular epithelial cell sodium transporters (Na-K-ATPase, Na-H exchange, Na- K-2C1 cotransport) in microdissected renal tubular segments. Mediation via DA D1 receptors will be evaluated with a specific D1 receptor antagonist (SCH23390). The interaction, additive or synergistic, with DA precursor agents (gludopa) and the effect on initiation, development and maintenance of hypertension will be examined.