Activation of D4 Dopamine Receptor Decreases Angiotensin II Type 1 Receptor Expression in Rat Renal Proximal Tubule Cells. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Chen, Ken; Deng, Kun; Wang, Xiaoyan; Wang, Zhen; Zheng, Shuo; Ren, Hongmei; He, Duofen; Han, Yu; Asico, Laureano D.; Jose, Pedro A.; Zeng, Chunyu
• Is Part Of: Hypertension. Volume 65:Issue 1(2015:Jan.)
• Publication Date: 2015-01
• Subjects: Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.114.04038
• Languages: English
• ISSNs: 0194-911X

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>The dopaminergic and renin–angiotensin systems interact to regulate blood pressure. Disruption of the D<sub>4</sub> dopamine receptor gene in mice produces hypertension that is associated with increased renal angiotensin type 1 (AT<sub>1</sub>) receptor expression. We hypothesize that the D<sub>4</sub> receptor can inhibit AT<sub>1</sub> receptor expression and function in renal proximal tubule cells from Wistar–Kyoto (WKY) rats, but the D<sub>4</sub> receptor regulation of AT<sub>1</sub> receptor is aberrant in renal proximal tubule cells from spontaneously hypertensive rats (SHRs). The D<sub>4</sub> receptor agonist, PD168077, decreased AT<sub>1</sub> receptor protein expression in a time- and concentration-dependent manner in WKY cells. By contrast, in SHR cells, PD168077 increased AT<sub>1</sub> receptor protein expression. The inhibitory effect of D<sub>4</sub> receptor on AT<sub>1</sub> receptor expression in WKY cells was blocked by a calcium channel blocker, nicardipine, or calcium-free medium, indicating that calcium is involved in the D<sub>4</sub> receptor–mediated signaling pathway. Angiotensin II increased Na<sup>+</sup>-K<sup>+</sup> ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effect of angiotensin II on Na<sup>+</sup>-K<sup>+</sup> ATPase activity in WKY cells. In SHR cells, the inhibitory effect of D<sub>4</sub> receptor on angiotensin II–mediated stimulation of Na<sup>+</sup>-K<sup>+</sup> ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT<sub>1</sub> receptor on Na<sup>+</sup>-K<sup>+</sup> ATPase activity in SHR cells. This was confirmed in vivo; pretreatment with PD128077 for 1 week augmented the antihypertensive and natriuretic effect of losartan in SHRs but not in WKY rats. We suggest that an aberrant interaction between D<sub>4</sub> and AT<sub>1</sub> receptors may play a role in the abnormal regulation of sodium excretion in hypertension.</p> </sec> </abstract>