DIFFERENTIAL HUMAN RENAL TUBULAR RESPONSES TO DOPAMINE TYPE-1 RECEPTOR STIMULATION ARE DETERMINED BY BLOOD-PRESSURE STATUS

We performed the present studies to determine whether a proximal renal tubular dopamine D-1-like receptor defect exists in human essential h ypertension. Twenty-four subjects were studied (13 normotensive and 11 hypertensive) in a randomized, double-blind, vehicle-controlled study using fenoldopam, a selective D-1-like receptor agonist. Subjects wer e studied in sodium metabolic balance at 300 mEq/d, after which the sa lt sensitivity of their blood pressure was determined. Fenoldopam at p eak doses of 0.1 to 0.2 mu g/kg per minute decreased mean arterial pre ssure in hypertensive subjects but did not change mean pressure in nor motensive subjects. Fenoldopam increased renal plasma flow to a greate r extent in hypertensive than normotensive subjects. Fenoldopam increa sed 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 reabsorpti on and sodium-potassium exchange fell significantly in hypertensive su bjects. We conclude that human essential hypertension is associated wi th a reduction in the proximal tubular response to D-1-like receptor s timulation compared with normotensive subjects. Hypertensive subjects appear to have a compensatory upregulation of renal vascular and dista l tubular D-1-like receptor function that offsets the proximal tubular defect, resulting in an enhanced natriuretic response to D-1-like rec eptor stimulation.