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) Supplemental Table and Figure All Versions of this Article: 293/5/E1134    most recent 00516.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Eringa, E. C. Articles by Sipkema, P. Search for Related Content PubMed PubMed Citation Articles by Eringa, E. C. Articles by Sipkema, P.

Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats

¹Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, Amsterdam; and ²Department of Internal Medicine, Academic Hospital Maastricht and University of Maastricht, Maastricht, The Netherlands

Submitted 25 September 2006 ; accepted in final form 9 July 2007

Obesity is related to insulin resistance and hypertension, but the underlying mechanisms are unclear. Insulin exerts both vasodilator and vasoconstrictor effects on muscle resistance arteries, which may be differentially impaired in obesity. Objectives: To investigate whether vasodilator and vasoconstrictor effects of insulin are impaired in muscle resistance arteries of obese rats and the roles of Akt and endothelial NO synthase (eNOS). Methods/Results: Effects of insulin were studied in resistance arteries isolated from cremaster muscles of lean and obese Zucker rats. In arteries of lean rats, insulin increased activity of both NO and endothelin (ET-1), resulting in a neutral effect under basal conditions. In arteries of obese rats, insulin induced endothelin-mediated vasoconstriction (–15 ± 5% at 1 nM, P < 0.05 vs. lean). Insulin induced vasodilatation during endothelin receptor blockade in arteries of lean rats (20 ± 5% at 1 nM) but not in those of obese rats. Inhibition of NO synthesis increased vascular tone (by 12 ± 2%) and shifted insulin-mediated vasoreactivity to vasoconstriction (–25 ± 1% at 1 nM) in lean rats but had no effect in arteries of obese rats, indicating reduced NO activity. Protein analysis of resistance arteries revealed that insulin-mediated activation of Akt was preserved in obese rats, whereas expression of eNOS was markedly decreased. Conclusions: Vasodilator but not vasoconstrictor effects of insulin are impaired in muscle resistance arteries of obese rats, and this selective impairment is associated with decreased protein levels of eNOS. These findings provide a new mechanism linking obesity to insulin resistance and hypertension.

microcirculation; obesity; hypertension; nitric oxide