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: 586/6/1669    most recent jphysiol.2007.150268v1 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 Raina, H. Articles by Hill, M. A. PubMed PubMed Citation Articles by Raina, H. Articles by Hill, M. A. Related Collections Cardiovascular

¹ School of Medical Sciences, RMIT University, Bundoora, Victoria 3083, Australia
² Dalton Cardiovascular Research Center, Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65211, USA
³ Department of Physiology and Pharmacology, University of New South Wales, Sydney, NSW 2052, Australia

Arteriolar myogenic vasoconstriction occurs when stretch or increased membrane tension leads to smooth muscle cell (SMC) depolarization and opening of voltage-gated Ca²⁺ channels. While the mechanism underlying the depolarization is uncertain a role for non-selective cation channels has been demonstrated. As such channels may be expected to pass Na⁺, we hypothesized that reverse mode Na⁺/Ca²⁺ exchange (NCX) may act to remove Na⁺ and in addition play a role in myogenic signalling through coupled Ca²⁺ entry. Further, reverse (Ca²⁺ entry) mode function of the NCX is favoured by the membrane potential found in myogenically active arterioles. All experiments were performed on isolated rat cremaster muscle first order arterioles (passive diameter 150 µm) which were pressurized in the absence of intraluminal flow. Reduction of extracellular Na⁺ to promote reverse-mode NCX activity caused significant, concentration-dependent vasoconstriction and increased intracellular Ca²⁺. This vasoconstriction was attenuated by the NCX inhibitors KB-R7943 and SEA 04000. Western blotting confirmed the existence of NCX protein while real-time PCR studies demonstrated that the major isoform expressed in the arteriolar wall was NCX1. Oligonucleotide knockdown (24 and 36 h) of NCX inhibited the vasoconstrictor response to reduced extracellular Na⁺ while also impairing both steady-state myogenic responses (as shown by pressure–diameter relationships) and acute reactivity to a 50 to 120 mmHg pressure step. The data are consistent with reverse mode activity of the NCX in arterioles and a contribution of this exchanger to myogenic vasoconstriction.

(Received 19 December 2007; accepted after revision 21 January 2008; first published online 24 January 2008)
Corresponding author M. A. Hill: Dalton Cardiovascular Research Center and Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65211, USA. Email: hillmi{at}missouri.edu