Channelpedia

PubMed 12574142


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir6.1



Title: Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: reduced activity of ATP-sensitive potassium channels.

Authors: Hiroto Miura, Ruth E Wachtel, Fausto R Loberiza, Takashi Saito, Mamoru Miura, Alfred C Nicolosi, David D Gutterman

Journal, date & volume: Circ. Res., 2003 Feb 7 , 92, 151-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12574142


Abstract
ATP-sensitive K+ channels (K(ATP)) contribute to vasomotor regulation in some species. It is not fully understood the extent to which K(ATP) participate in regulating vasomotor tone under physiological and pathophysiological conditions in the human heart. Arterioles dissected from right atrial appendage were studied with video microscopy, membrane potential recordings, reverse transcription-polymerase chain reaction, and immunohistochemistry. Hypoxia produced endothelium-independent vasodilation and membrane hyperpolarization of vascular smooth muscle cells, both of which were attenuated by glibenclamide. Aprikalim, a selective K(ATP) opener, also induced a potent endothelium-independent and glibenclamide-sensitive vasodilation with membrane hyperpolarization. Reverse transcription-polymerase chain reaction detected mRNA expression for K(ATP) subunits, and immunohistochemistry confirmed the localization of the inwardly rectifying Kir6.1 protein in the vasculature. In patients with type 1 or type 2 diabetes mellitus (DM), vasodilation was reduced to both aprikalim (maximum dilation, DM(+) 90+/-2% versus DM(-) 96+/-1%, P<0.05) and hypoxia (maximum dilation, DM(+) 56+/-8% versus DM(-) 85+/-5%, P<0.01) but was not altered to sodium nitroprusside or bradykinin. Baseline myogenic tone and resting membrane potential were not affected by DM. We conclude that DM impairs human coronary arteriolar dilation to K(ATP) opening, leading to reduced dilation to hypoxia. This reduction in K(ATP) function could contribute to the greater cardiovascular mortality and morbidity in DM.