Role of potassium channels in the vascular response to endogenous and pharmacological vasodilators.
Many endogenous and pharmacological vasodilators hyperpolarize vascular smooth muscle and this response appears to be due to an increased conductance to potassium ions. The hyperpolarization may contribute to the mechanism of dilation by causing voltage-dependent calcium channels to close. Recent evidence indicates that the response to hyperpolarizing vasodilators is mediated through activation of ATP-sensitive potassium (KATP) channels. Single KATP channels on isolated vascular smooth muscle cells are activated by cromakalim and calcitonin gene-related peptide (CGRP). This response is inhibited by glibenclamide. Cromakalim, CGRP and other vasodilators hyperpolarize and relax arteries in vitro and these responses are reversed by glibenclamide. The hypotensive effects of these agents in vivo are antagonized by glibenclamide. We propose that activation of KATP channels and the associated membrane hyperpolarization represents an important general mechanism of vasodilation.
Brayden
J E
JE
Department of Pharmacology, College of Medicine, University of Vermont, Burlington.
Quayle
J M
JM
Standen
N B
NB
Nelson
M T
MT
D000818:Animals; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents