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Submitted on November 10, 2003
From Institute of Physiology (R.S., U.K., G.L.), University Rostock, Germany; Institute of Physiology (I.W., D.S., J.R.S.), University Hamburg, Germany; Institute of Anatomy (N.U.), RG Neuroembryology, University Rostock, Germany; Institute of Anatomy (R.W.V.), Charite, Humboldt-University, Berlin, Germany; Institute of Biophysics (H.G.), Bulgarian Academy of Sciences, Sofia, Bulgaria. * To whom correspondence should be addressed. E-mail: rudolf.schubert{at}medizin.uni-rostock.de.
Abstract--The role of vascular smooth muscle inward rectifier K+ (KIR) channels in the mechanisms underlying vasodilation is still unclear. The hypothesis that KIR channels are involved in sodium nitroprusside (SNP)-induced dilation of rat-tail small arteries was tested. SNP relaxed tail small arteries with an EC50 of 2.6x10-8 mol/L. Endothelium removal did not attenuate this effect. Vessel pretreatment with hydroxocobalamin, a nitric oxide (NO) scavenger, but not with rhodanese and sodium thiosulfate, inactivators of cyanide (CN), abolished the SNP effect. Vessel pretreatment with 10-5 mol/L Ba2+, a specific blocker of KIR channels at micromolar concentrations, reduced the SNP effect. Low concentrations of K+ dilated the vessels; this effect was attenuated largely after pretreatment with 3x10-5 mol/L Ba2+. In freshly isolated smooth muscle cells, a barium-sensitive current was observed at potentials negative to the potassium equilibrium potential. Application of 10-4 mol/L SNP increased the barium-sensitive current 1.79±0.23-fold at -100 mV and hyperpolarized the membrane potential by 8.6±0.5 mV. In tissue from freshly dissected vessels, transcripts for KIR 2.1 and 2.2, but not for KIR 2.3 and 2.4, were found. However, only KIR 2.1 antibodies immunostained the tunica media of the vessel. These data suggest that vascular smooth muscle KIR 2.1 channels are involved in the SNP-induced dilation of rat-tail small arteries.
Revised on December 1, 2003
Nitric Oxide Donor Sodium Nitroprusside Dilates Rat Small Arteries by Activation of Inward Rectifier Potassium Channels
Rudolf Schubert*;
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