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This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/F1430    most recent 00218.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Hakam, A. C. Articles by Hussain, T. Search for Related Content PubMed PubMed Citation Articles by Hakam, A. C. Articles by Hussain, T.

Angiotensin II AT₂ receptors inhibit proximal tubular Na⁺-K⁺-ATPase activity via a NO/cGMP-dependent pathway

Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas

Submitted 24 May 2005 ; accepted in final form 23 December 2005

Angiotensin II AT₂ receptors act as a functional antagonist for the AT₁ receptors in various tissues. We previously reported that activation of the renal AT₂ receptors promotes natriuresis and diuresis; however, the mechanism is not known. The present study was designed to investigate whether activation of AT₂ receptors affects the activity of Na⁺-K⁺-ATPase (NKA), an active tubular sodium transporter, in the proximal tubules isolated from Sprague-Dawley rats. The AT₂ receptor agonist CGP-42112 (10^–10-10^–7 M) produced a dose-dependent inhibition of NKA activity (9–38%); the inhibition was attenuated by the presence of the AT₂ receptor antagonist PD-123319 (1 µM), suggesting the involvement of the AT₂ receptors. The AT₁ receptor antagonist losartan (1 µM) did not affect the CGP-42112 (100 nM)-induced inhibition of NKA activity. The presence of guanylyl cyclase inhibitor ODQ (10 µM) and the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME; 100 µM) abolished the CGP-42112 (100 nM)-induced NKA inhibition. ANG II (100 nM), in the presence of losartan, significantly inhibited NKA activity; the inhibition was attenuated by PD-123319. CGP-42112 also, in a dose-dependent manner, stimulated NO production (0–230%) and cGMP accumulation (25–100%). The CGP-42112 (100 nM)-induced NO and cGMP increases were abolished by the AT₂ receptor antagonist PD-123319, ODQ, and L-NAME. The data suggest that the activation of the AT₂ receptor via stimulation of the NO/cGMP pathway causes inhibition of NKA activity in the proximal tubules. This phenomenon provides a plausible mechanism responsible for the AT₂ receptor-mediated natriuresis-diuresis in rodents.

kidney; sodium transport; natriuresis

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