2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2008090943v1 20/7/1577    most recent 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 Google Scholar Articles by Just, A. Articles by Arendshorst, W. J. PubMed PubMed Citation Articles by Just, A. Articles by Arendshorst, W. J.

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

Armin Just^*,, Lisa Kurtz, Cor de Wit, Charlotte Wagner^||, Armin Kurtz^|| and William J. Arendshorst^*,,¶

^* Department of Cell & Molecular Physiology, Carolina Cardiovascular Biology Center, and ^¶ University of North Carolina Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; ^|| Physiologisches Institut der Universität Regensburg, Regensburg, Germany; and Physiologisches Institut der Universität Lübeck, Lübeck, Germany; Klink für Innere Medizin II, Universität Regensburg, Regensburg, Germany

Correspondence: Dr. Armin Just, Physiologisches Institut, Abt. I, Albert-Ludwigs-Universität Freiburg, Engesser Strasse 4, 79108 Freiburg, Germany. Phone: +49-761-203-5198; Fax: +49-761-203-5204; E-mail: armin.just{at}physiologie.uni-freiburg.de

Received for publication September 7, 2008. Accepted for publication March 5, 2009.

Connexins are important in vascular development and function. Connexin 40 (Cx40), which plays a predominant role in the formation of gap junctions in the vasculature, participates in the autoregulation of renal blood flow (RBF), but the underlying mechanisms are unknown. Here, Cx40-deficient mice (Cx40-ko) had impaired steady-state autoregulation to a sudden step increase in renal perfusion pressure. Analysis of the mechanisms underlying this derangement suggested that a marked reduction in tubuloglomerular feedback (TGF) in Cx40-ko mice was responsible. In transgenic mice with Cx40 replaced by Cx45, steady-state autoregulation and TGF were weaker than those in wild-type mice but stronger than those in Cx40-ko mice. N-Nitro-L-arginine-methyl-ester (L-NAME) augmented the myogenic response similarly in all genotypes, leaving autoregulation impaired in transgenic animals. The responses of renovascular resistance and arterial pressure to norepinephrine and acetylcholine were similar in all groups before or after L-NAME inhibition. Systemic and renal vasoconstrictor responses to L-NAME were also similar in all genotypes. We conclude that Cx40 contributes to RBF autoregulation by transducing TGF-mediated signals to the afferent arteriole, a function that is independent of nitric oxide (NO). However, Cx40 is not required for the modulation of the renal myogenic response by NO, norepinephrine-induced renal vasoconstriction, and acetylcholine- or NO-induced vasodilation.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673