Perturbation of D-1 dopamine and AT(1) receptor interaction in spontaneously hypertensive rats

The dopaminergic and renin-angiotensin systems interact to regulate blood pressure. Because this interaction may be perturbed in genetic hypertension, we studied D-1 dopamine and AT(1) angiotensin receptors in immortalized renal proximal tubule (RPT) and A10 aortic vascular smooth muscle cells. In normotensive Wistar-Kyoto (WKY) rats, the D-1-like agonist fenoldopam increased D-1 receptors but decreased AT(1) receptors. These effects were blocked by the D-1-like antagonist SCH 23390 (10(-7) mol/L per 24 hours). In spontaneously hypertensive rat (SHR) RPT cells, fenoldopam also decreased AT(1) receptors but no longer stimulated D-1 receptor expression. Basal levels of AT(1)/D-1 receptor coimmunoprecipitation were greater in WKY RPT cells (29 +/- 2 density units, DU) than in SHR RPT cells (21 +/- 2 DU, n = 7 per group, P < 0.05). The coimmunoprecipitation of D-1 and AT(1) receptors was increased by fenoldopam (10(-7) mol/L per 24 hours) in WKY RPT cells but decreased in SHR RPT cells. The effects of fenoldopam in RPT cells from WKY rats were similar in aortic vascular smooth muscle cells from normotensive BD IX rats, that is, fenoldopam decreased AT(1) receptors and increased D-1 receptors. Our studies show differential regulation of the expression of D-1 and AT(1) receptors in RPT cells from WKY and SHR. This regulation and D-1/AT(1) receptor interaction are different in RPT cells of WKY and SHR. An altered interaction of D-1 and AT(1) receptors may play a role in the impaired sodium excretion and enhanced vasoconstriction in hypertension.