Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: reduced activity of ATP-sensitive potassium channels. Circ Res 2003 Feb 07;92(2):151-8
Date
02/08/2003Pubmed ID
12574142DOI
10.1161/01.res.0000052671.53256.49Scopus ID
2-s2.0-0037423556 (requires institutional sign-in at Scopus site) 152 CitationsAbstract
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.
Author List
Miura H, Wachtel RE, Loberiza FR Jr, Saito T, Miura M, Nicolosi AC, Gutterman DDMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAge Factors
Arterioles
Bradykinin
Coronary Vessels
Diabetes Mellitus
Female
Glyburide
Humans
Hypoxia
In Vitro Techniques
Male
Membrane Potentials
Microcirculation
Middle Aged
Muscle, Smooth, Vascular
Nitric Oxide Donors
Picolines
Potassium Channels
Potassium Channels, Inwardly Rectifying
Pyrans
RNA, Messenger
Risk Factors
Sex Factors
Vasodilation
Vasodilator Agents
