期刊
HYPERTENSION
卷 41, 期 3, 页码 724-729出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.0000047880.78462.0E
关键词
receptors, dopamine; receptors, angiotensin II; rats, spontaneously hypertensive; kidney
资金
- NHLBI NIH HHS [HL 23081, HL68686, HL 62211] Funding Source: Medline
- NIDDK NIH HHS [DK 39308, DK52612] Funding Source: Medline
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(-8)M/24 hours) decreased D-3 receptors in both normotensive (control, 36+/-3; angiotensin II, 24+/-3 U) and hypertensive (control, 30+/-3; angiotensin II, 11+/-3 U; n=9 per group) rats; effects that were blocked by the AT(1) receptor antagonist, losartan (10(-8)M/24 hours). However, the reduction in D-3 expression was greater in hypertensive (60+/-10%) than in normotensive rats (32+/-9%). In normotensive rats, angiotensin II (10(-8)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.
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