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: 568/2/483    most recent jphysiol.2005.085019v1 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 Robert, R. Articles by Becq, F. Search for Related Content PubMed PubMed Citation Articles by Robert, R. Articles by Becq, F.

¹ Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Université de Poitiers, 40 Avenue du Recteur Pineau, 86022 Poitiers, France

Chloride (Cl^–) channels expressed in vascular smooth muscle cells (VSMC) are important to control membrane potential equilibrium, intracellular pH, cell volume maintenance, contraction, relaxation and proliferation. The present study was designed to compare the expression, regulation and function of CFTR Cl^– channels in aortic VSMC from Cftr^+/+ and Cftr^–/– mice. Using an iodide efflux assay we demonstrated stimulation of CFTR by VIP, isoproterenol, cAMP agonists and other pharmacological activators in cultured VSMC from Cftr^+/+. On the contrary, in cultured VSMC from Cftr^–/– mice these agonists have no effect, showing that CFTR is the dominant Cl^– channel involved in the response to cAMP mediators. Angiotensin II and the calcium ionophore A23187 stimulated Ca²⁺-dependent Cl^– channels in VSMCs from both genotypes. CFTR was activated in myocytes maintained in medium containing either high potassium or 5-hydroxytryptamine (5-HT) and was inhibited by CFTR_inh-172, glibenclamide and diphenylamine-2,2'-dicarboxylic acid (DPC). We also examined the mechanical properties of aortas. Arteries with or without endothelium from Cftr^–/– mice became significantly more constricted (2-fold) than that of Cftr^+/+ mice in response to vasoactive agents. Moreover, in precontracted arteries of Cftr^+/+ mice, VIP and CFTR activators induced vasorelaxation that was altered in Cftr^–/– mice. Our findings suggest a novel mechanism for regulation of the vascular tone by cAMP-dependent CFTR chloride channels in VSMC. To our knowledge this study is the first to report the phenotypic consequences of the loss of a Cl^– channel on vascular reactivity.

(Received 22 July 2005; accepted after revision 3 August 2005; first published online 4 August 2005)
Corresponding author F. Becq: IPBC, CNRS UMR 6187, Université de Poitiers, 40 Avenue du Recteur Pineau, 86022 Poitiers, France. Email: frederic.becq{at}univ-poitiers.fr

This article has been cited by other articles:

				R. Robert, J-P. Savineau, C. Norez, F. Becq, and C. Guibert Expression and function of cystic fibrosis transmembrane conductance regulator in rat intrapulmonary arteries Eur. Respir. J., November 1, 2007; 30(5): 857 - 864. [Abstract] [Full Text] [PDF]