HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 20, 17963-17968, May 16, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/20/17963    most recent M213113200v1 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 Google Scholar Google Scholar Articles by Sabrane, K. Articles by Kuhn, M. Search for Related Content PubMed PubMed Citation Articles by Sabrane, K. Articles by Kuhn, M. Social Bookmarking                      What's this?

Increased Sensitivity to Endothelial Nitric Oxide (NO) Contributes to Arterial Normotension in Mice with Vascular Smooth Muscle-selective Deletion of the Atrial Natriuretic Peptide (ANP) Receptor^*

Karim Sabrane, Stepan Gambaryan^§, Ralf P. Brandes^¶, Rita Holtwick, Melanie Voss, and Michaela Kuhn

From the  Institute of Pharmacology and Toxicology, Universitätsklinikum Münster, D-48149 Münster, Germany, the ^§ Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany, and the ^¶ Institute of Cardiovascular Physiology, Klinikum der J. W. Goethe-Universität, 60590 Frankfurt/Main, Germany

Atrial natriuretic peptide (ANP) plays a key regulatory role in arterial blood pressure homeostasis. We recently generated mice with selective deletion of the ANP receptor, guanylyl cyclase-A (GC-A), in vascular smooth muscle (SMC GC-A knockout (KO) mice) and reported that resting arterial blood pressure was completely normal in spite of clear abolition of the direct vasodilating effects of ANP (Holtwick, R., Gotthardt, M., Skryabin, B., Steinmetz, M., Potthast, R., Zetsche, B., Hammer, R. E., Herz, J., and Kuhn M. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 7142-7147). The purpose of this study was to clarify mechanisms compensating for the missing vasodilator responses to ANP. In particular, we analyzed the effect of the endothelial, cGMP-mediated vasodilators C-type natriuretic peptide and nitric oxide (NO). In isolated arteries from SMC GC-A KO mice, the vasorelaxing sensitivity to sodium nitroprusside and the endothelium-dependent vasodilator, acetylcholine, was significantly greater than in control mice. There was no difference in responses to C-type natriuretic peptide or to the activator of cGMP-dependent protein kinase I, 8-para-chlorophenylthio-cGMP. The aortic expression of soluble GC (sGC), but not of endothelial NO synthase or cGMP-dependent protein kinase I, was significantly increased in SMC GC-A KO mice. Chronic oral treatment with the NO synthase inhibitor N^w-nitro-L-arginine methyl ester increased arterial blood pressure, the effect being significantly enhanced in SMC GC-A KO mice. We conclude that SMC GC-A KO mice exhibit a higher vasodilating sensitivity to NO. This can be attributed to an enhanced expression of sGC, whereas the expression and/or activity levels of downstream cGMP-effector pathways are not involved. Increased vasodilating responsiveness to endothelial NO contributes to compensate for the missing vasodilating effect of ANP in SMC GC-A KO mice.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. L. Marro, C. Peiro, C. M. Panayiotou, R. S. Baliga, S. Meurer, H. H. H. W. Schmidt, and A. J. Hobbs Characterization of the Human {alpha}1{beta}1 Soluble Guanylyl Cyclase Promoter: KEY ROLE FOR NF-{kappa}B(p50) AND CCAAT-BINDING FACTORS IN REGULATING EXPRESSION OF THE NITRIC OXIDE RECEPTOR J. Biol. Chem., July 18, 2008; 283(29): 20027 - 20036. [Abstract] [Full Text] [PDF]

				S. M. Fitzgerald, B. K. Kemp-Harper, H. C. Parkington, G. A. Head, and R. G. Evans Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R707 - R713. [Abstract] [Full Text] [PDF]