title: Perturbation of D1 dopamine and AT1 receptor interaction in spontaneously hypertensive rats.
abstract: The dopaminergic and renin-angiotensin systems interact to regulate blood pressure. Because this interaction may be perturbed in genetic hypertension, we studied D1 dopamine and AT1 angiotensin receptors in immortalized renal proximal tubule (RPT) and A10 aortic vascular smooth muscle cells. In normotensive Wistar-Kyoto (WKY) rats, the D1-like agonist fenoldopam increased D1 receptors but decreased AT1 receptors. These effects were blocked by the D1-like antagonist SCH 23390 (10(-7) mol/L per 24 hours). In spontaneously hypertensive rat (SHR) RPT cells, fenoldopam also decreased AT1 receptors but no longer stimulated D1 receptor expression. Basal levels of AT1/D1 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 D1 and AT1 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 AT1 receptors and increased D1 receptors. Our studies show differential regulation of the expression of D1 and AT1 receptors in RPT cells from WKY and SHR. This regulation and D1/AT1 receptor interaction are different in RPT cells of WKY and SHR. An altered interaction of D1 and AT1 receptors may play a role in the impaired sodium excretion and enhanced vasoconstriction in hypertension.
authors.affiliation: Department of Pediatrics, Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20007, USA. cyzeng1@hotmail.com
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
authors.forename: Yingjin
authors.initials: Y
authors.lastname: Luo
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hopfer
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Eisner
authors.forename: Robin A
authors.initials: RA
authors.lastname: Felder
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology; D018818:Fenoldopam / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011233:Precipitin Tests; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D017447:Receptors, Dopamine D1; D018818:Fenoldopam