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(Hypertension. 1997;29:115.)
© 1997 American Heart Association, Inc.

Research Articles (Issue 1, Part 1)

Differential Human Renal Tubular Responses to Dopamine Type 1 Receptor Stimulation Are Determined by Blood Pressure Status

Damian P. O'Connell; N. Virginia Ragsdale; David G. Boyd; Robin A. Felder; Robert M. Carey

the Department of Pharmacology and Therapeutics, University College Cork (Ireland) (D.P.O'C.), and the Departments of Medicine and Pathology, University of Virginia Health Sciences Center, Charlottesville.

Correspondence to Dr Robert M. Carey, Box 395, University of Virginia Health Sciences Center, Charlottesville, VA 22908. E-mail rmc4c@virginia.edu.

We performed the present studies to determine whether a proximal renal tubular dopamine D₁-like receptor defect exists in human essential hypertension. Twenty-four subjects were studied (13 normotensive and 11 hypertensive) in a randomized, double-blind, vehicle-controlled study using fenoldopam, a selective D₁-like receptor agonist. Subjects were studied in sodium metabolic balance at 300 mEq/d, after which the salt sensitivity of their blood pressure was determined. Fenoldopam at peak doses of 0.1 to 0.2 µg/kg per minute decreased mean arterial pressure in hypertensive subjects but did not change mean pressure in normotensive subjects. Fenoldopam increased renal plasma flow to a greater extent in hypertensive than normotensive subjects. Fenoldopam increased both urinary and fractional sodium excretions in the hypertensive and normotensive groups. In normotensive but not hypertensive subjects, fenoldopam increased the fractional excretion of lithium and distal sodium delivery. In contrast, both distal fractional sodium reabsorption and sodium-potassium exchange fell significantly in hypertensive subjects. We conclude that human essential hypertension is associated with a reduction in the proximal tubular response to D₁-like receptor stimulation compared with normotensive subjects. Hypertensive subjects appear to have a compensatory upregulation of renal vascular and distal tubular D₁-like receptor function that offsets the proximal tubular defect, resulting in an enhanced natriuretic response to D₁-like receptor stimulation.

Key Words: receptors, dopamine • blood pressure • kidney tubules, proximal • dopamine agonists

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