Dopamine and angiotensin II negatively interact to regulate sodium excretion and blood pressure. D 3 dopamine receptors downregulate angiotensin type 1 (AT 1 ) receptors in renal proximal tubule cells from normotensive Wistar-Kyoto rats. We determined whether AT 1 receptors regulate D 3 receptors and whether the regulation is different in cultured renal proximal tubule cells from normotensive and spontaneously hypertensive rats. Angiotensin II (10 Ϫ8 M/24 hours) decreased D 3 receptors in both

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... ormotensive (control, 36Ϯ3; angiotensin II, 24Ϯ3 U) and hypertensive (control, 30Ϯ3; angiotensin II, 11Ϯ3 U; nϭ9 per group) rats; effects that were blocked by the AT 1 receptor antagonist, losartan (10 Ϫ8 M/24 hours). However, the reduction in D 3 expression was greater in hypertensive (60Ϯ10%) than in normotensive rats (32Ϯ9%). In normotensive rats, angiotensin II (10 Ϫ8 M/24hr) also decreased AT 1 receptors. In contrast, in cells from hypertensive rats, angiotensin II increased AT 1 receptors. AT 1 and D 3 receptors coimmunoprecipitated in renal proximal tubule cells from both strains. Angiotensin II decreased D 3 /AT 1 receptor co-immunoprecipitation similarly in both rat strains, but basal D 3 /AT 1 co-immunoprecipitation was 6 times higher in normotensive than in hypertensive rats. Therefore, AT 1 and D 3 receptor interaction is qualitatively and quantitatively different between normotensive and hypertensive rats; angiotensin II decreases AT 1 expression in normotensive but increases it in hypertensive rats. In addition, angiotensin II decreases D 3 expression to a greater extent in hypertensive than in normotensive rats. Aberrant interactions between D 3 and AT 1 receptors may play a role in the pathogenesis of hypertension. (Hypertension. 2003;41[part 2]:724-729.)