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

This Article Full Text Full Text (PDF) All Versions of this Article: 287/2/R342    most recent 00156.2004v1 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 Web of Science 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 Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Budzyn, K. Articles by Sobey, C. G. Search for Related Content PubMed PubMed Citation Articles by Budzyn, K. Articles by Sobey, C. G.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Chronic mevastatin modulates receptor-dependent vascular contraction in eNOS-deficient mice

Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia

Submitted 10 March 2004 ; accepted in final form 22 April 2004

We tested the hypothesis that endothelial nitric oxide (NO) synthase (eNOS)-derived NO modulates rho-kinase-mediated vascular contraction. Because 3-hydroxy-3-methylglutaryl (HMG)-CoA-reductase inhibition can both upregulate eNOS expression and inhibit rhoA/rho-kinase function, a second hypothesis tested was that statin treatment modulates rho-kinase-mediated contraction and that this can occur independently of eNOS. Contractile responses to the receptor-dependent agonists serotonin and phenylephrine but not to the receptor-independent agent KCl were greater in aortic rings from eNOS-null (eNOS^–/–) vs. wild-type (eNOS^+/+) mice. Similarly enhanced responses were seen in eNOS^+/+ rings after acute NOS inhibition. The rho-kinase inhibitor Y-27632 abolished or profoundly attenuated responses to receptor agonists in both eNOS^+/+ and eNOS^–/– rings, but responses in eNOS^+/+ were more sensitive to Y-27632. Mevastatin treatment (20 mg/kg sc per day, 14 days) reduced responses to serotonin and phenylephrine in female mice of both strains. KCl-induced contractions were slightly smaller in eNOS^+/+-derived aortic rings only. Levels of plasma cholesterol, and aortic expression of rhoA and rho-kinase, did not differ between groups. Thus eNOS-derived NO suppresses rhoA/rho-kinase-mediated vascular contraction. Moreover, a similar suppressive effect on rho-kinase-mediated vasoconstriction by statin therapy occurs independently of effects on eNOS or plasma cholesterol.

endothelium; vasoconstriction; statins

This article has been cited by other articles:

				M. F. Kircher, J. Grimm, F. K. Swirski, P. Libby, R. E. Gerszten, J. R. Allport, and R. Weissleder Noninvasive In Vivo Imaging of Monocyte Trafficking to Atherosclerotic Lesions Circulation, January 22, 2008; 117(3): 388 - 395. [Abstract] [Full Text] [PDF]

				S. Chrissobolis and C. G. Sobey Recent Evidence for an Involvement of Rho-Kinase in Cerebral Vascular Disease Stroke, August 1, 2006; 37(8): 2174 - 2180. [Abstract] [Full Text] [PDF]

				K. Budzyn, P. D. Marley, and C. G. Sobey Opposing Roles of Endothelial and Smooth Muscle Phosphatidylinositol 3-Kinase in Vasoconstriction: Effects of Rho-Kinase and Hypertension J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1248 - 1253. [Abstract] [Full Text] [PDF]