Angiotensin II Regulation of AT1 and D3 Dopamine Receptors in Renal Proximal Tubule Cells of SHR

C. Zeng, L. D. Asico, X. Wang, U. Hopfer, G. M. Eisner, R. A. Felder, P. A. Jose
2002 Hypertension  
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
more » ... 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.)
doi:10.1161/01.hyp.0000047880.78462.0e pmid:12623987 fatcat:ximjd4hoezbgflnf3bfxzlh4om