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Submitted on July 10, 2002
Revised on December 6, 2002
Accepted on December 6, 2002
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.
* To whom correspondence should be addressed. 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 participates 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 transcriptase-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 transcriptase-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.
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