Published online before print December 19, 2002, doi: 10.1161/01.RES.0000052671.53256.49
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© 2003 American Heart Association, Inc.
Clinical Research |
Diabetes Mellitus Impairs Vasodilation to Hypoxia in Human Coronary Arterioles
Reduced Activity of ATP-Sensitive Potassium Channels
From the Department of Veterans Affairs Medical Center (H.M., D.D.G.), Milwaukee, Wis; Department of Veterans Affairs Medical Center (R.E.W.) and Department of Anesthesia, University of Iowa College of Medicine (R.E.W.), Iowa City, Iowa; Department of Medicine and Cardiovascular Research Center (H.M., D.D.G.), Health Policy Institute (F.R.L.), and Department of Surgery (A.C.N.), Medical College of Wisconsin, Milwaukee, Wis; and 2nd Department of Internal Medicine (T.S., M.M.), Akita University, Akita City, Japan.
Correspondence to Hiroto Miura, Department of Medicine and Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail hmiura{at}mcw.edu
ATP-sensitive K+ channels (KATP) contribute to vasomotor regulation in some species. It is not fully understood the extent to which KATP 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 KATP opener, also induced a potent endothelium-independent and glibenclamide-sensitive vasodilation with membrane hyperpolarization. Reverse transcription–polymerase chain reaction detected mRNA expression for KATP 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 KATP opening, leading to reduced dilation to hypoxia. This reduction in KATP function could contribute to the greater cardiovascular mortality and morbidity in DM.
Key Words: human • coronary microcirculation • ATP-sensitive potassium channels • hypoxia • diabetes mellitus
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