Nitric oxide donor sodium nitroprusside dilates rat small arteries by activation of inward rectifier potassium channels.
The role of vascular smooth muscle inward rectifier K+ (K(IR)) channels in the mechanisms underlying vasodilation is still unclear. The hypothesis that K(IR) 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 K(IR) 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 K(IR) 2.1 and 2.2, but not for K(IR) 2.3 and 2.4, were found. However, only K(IR) 2.1 antibodies immunostained the tunica media of the vessel. These data suggest that vascular smooth muscle K(IR) 2.1 channels are involved in the SNP-induced dilation of rat-tail small arteries.
Institute of Physiology, University Rostock, Rostock, Germany. rudolf.schubert@medizin.uni-rostock.de
Rudolf
R
Schubert
Ulrike
U
Krien
Iris
I
Wulfsen
Dorrit
D
Schiemann
Gernot
G
Lehmann
Norbert
N
Ulfig
Ruediger W
RW
Veh
Jürgen R
JR
Schwarz
Hristo
H
Gago
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001464:Barium / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006879:Hydroxocobalamin / Q000494:pharmacology; D017136:Ion Transport; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D013623:Tail / Q000098:blood supply; D013884:Thiosulfate Sulfurtransferase / Q000494:pharmacology; D013885:Thiosulfates / Q000494:pharmacology; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D024661:Potassium Channels, Inwardly Rectifying; D013885:Thiosulfates; D014665:Vasodilator Agents; D009599:Nitroprusside; D001464:Barium; D009569:Nitric Oxide; D013884:Thiosulfate Sulfurtransferase; C017717:sodium thiosulfate; D006879:Hydroxocobalamin; D011188:Potassium