Nitric oxide inhibits the expression of AT1 receptors in neurons

Neeru M. Sharma; Hong Zheng; Yi-Fan Li; Kaushik P. Patel

doi:10.1152/ajpcell.00258.2011

$We have previously observed an increased of angiotensin II (ANG II) type 1 receptor (AT 1 R) with enhanced AT 1 R-mediated sympathetic outflow and concomitant downregulation of neuronal nitric oxide (NO) synthase (nNOS) with reduced NO-mediated inhibition from the paraventricular nucleus (PVN) in rats with heart failure. To test the hypothesis that NO exerts an inhibitory effect on AT 1 R expression in the PVN, we used primary cultured hypothalamic cells of neonatal rats and neuronal cell line NG108-15 as in vitro models. In hypothalamic primary culture, NO donor sodium nitroprusside (SNP) induced dose-dependent decreases in mRNA and protein of AT 1 R (10 −5 M SNP, AT 1 R protein was 10 ± 2% of control level) while NOS inhibitor N G -monomethyl- l -arginine ( l -NMMA) induced dose-dependent increases in mRNA and protein levels of AT 1 R (10 −5 M l -NMMA, AT 1 R protein was 148 ± 8% of control level). Similar effects of SNP and l -NMMA on AT 1 R expression were also observed in NG108-15 cell line (10 −6 M SNP, AT 1 R protein was 30 ± 4% of control level while at the dose of 10 −6 M l -NMMA, AT 1 R protein was 171 ± 15% of the control level). Specific inhibition of nNOS, using antisense, caused an increase in AT 1 R expression while overexpression of nNOS, using adenoviral gene transfer (Ad.nNOS), caused an inhibition of AT 1 R expression in NG108 cells. Antisense nNOS transfection augmented the increase while Ad.nNOS infection blunted the increase in intracellular calcium concentration in response to ANG II treatment in NG108 cells. In addition, downregulation of AT 1 R mRNA as well as protein level in neuronal cell line in response to S -nitroso- N -acetyl pencillamine (SNAP) treatment was blocked by protein kinase G (PKG) inhibitor, while the peroxynitrite scavenger deforxamine had no effect. These results suggest that NO acts as an inhibitory regulator of AT 1 R expression and the activation of PKG is the required step in the regulation of AT 1 R gene expression via cGMP-dependent signaling pathway. sympathetic nerve activity angiotensin II cGMP protein kinase G « Previous | Next Article » Table of Contents This Article Published online before print January 4, 2012 , doi: 10.1152/ajpcell.00258.2011 Am J Physiol Cell Physiol April 15, 2012 vol. 302 no. 8 C1162-C1173 » Abstract Free Full Text Free Full Text (PDF) Free All Versions of this Article: ajpcell.00258.2011v1 302/8/C1162 most recent Classifications Receptors and Signal Transduction Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Sharma, N. M. Articles by Patel, K. P. PubMed PubMed citation Articles by Sharma, N. M. Articles by Patel, K. P. Related Content Load related web page information Current Content Alert me to new issues of Am J Physiol Cell Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6143 Online ISSN: 1522-1563 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview(); } catch(err) {} var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-189672-30"); pageTracker._setDomainName(".physiology.org"); pageTracker._trackPageview(); } catch(err) {}$

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Nitric oxide inhibits the expression of AT1 receptors in neurons

Sharma, Neeru M.; Zheng, Hong; Li, Yi-Fan; Patel, Kaushik P.

Follow AJP - Cell Physiology , Volume 302 (8): C1162 The American Physiological Society – Apr 15, 2012

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Nitric oxide inhibits the expression of AT1 receptors in neurons

Sharma, Neeru M.; Zheng, Hong; Li, Yi-Fan; Patel, Kaushik P.

Follow AJP - Cell Physiology , Volume 302 (8): C1162 The American Physiological Society – Apr 15, 2012

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