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Contribution of Na+ -Ca2+ exchanger to pinacidil-induced relaxation in the rat mesenteric artery.

Abstract：

:1 Pinacidil relaxes blood vessels through opening the K(ATP) channels with a resultant membrane hyperpolarization and inhibition of Ca(2+) influx. The aim of this study was to examine the mechanisms thereby pinacidil induces K(+) channel-independent relaxation in isolated endothelium-denuded rat mesenteric artery. 2 Pinacidil-induced relaxation was inhibited by glibenclamide (1-10 micro M) in phenylephrine-preconstricted rings, but was unaffected by glibenclamide after inhibition of K(+) channels and VGCCs. Pinacidil-induced K(+) channel-independent relaxation remained unchanged after treatment with cyclopiazonic acid (10 micro M), thapsigargin (1 micro M), ouabain (100 micro M), propranolol (10 micro M), Rp-cAMPS triethylamine (30 micro M), L-NNA (100 micro M), or ODQ (10 micro M). 3 Pinacidil induced more relaxant effect in the presence of nifedipine than in the presence of 60 mM K(+) plus nifedipine. Pretreatment with Na(+)-Ca(2+) exchanger inhibitors, nickel (30-300 micro M) or benzamil (20 micro M) attenuated pinacidil-induced relaxation in normal or in nifedipine-containing solution. Pinacidil (1 micro M) produced less relaxant effect with decreasing extracellular Na(+) concentration. Na(+)-free condition abolished the inhibitory effect of benzamil. Both nickel and benzamil inhibited pinacidil-induced relaxation in the presence of glibenclamide (10 micro M). Nickel (300 micro M) did not affect the relaxant response to sodium nitroprusside. 4 Pinacidil relaxed the rings preconstricted by active phorbol and U46619 with similar potency. 5 The present results indicate that stimulation of the forward mode Na(+)-Ca(2+) exchange pathway is in part responsible for pinacidil-induced K(+) channel-independent vasorelaxation. Pinacidil also induces K(+) channel-dependent but VGCCs-independent relaxation. The PKC-mediated cellular pathway may be a target site for pinacidil only in higher concentrations.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Tsang SY,Yao X,Wong CM,Au CL,Chen ZY,Huang Y

doi

10.1038/sj.bjp.0705062

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

453-60

issue

eissn

0007-1188

issn

1476-5381

journal_volume

138

pub_type

杂志文章

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Contribution of Na+ -Ca2+ exchanger to pinacidil-induced relaxation in the rat mesenteric artery.