Diabetes Mellitus Impairs Vasodilation to Hypoxia in Human Coronary Arterioles: Reduced Activity of ATP-Sensitive Potassium Channels

• Published in: Circulation research 2003-02, Vol.92 (2), p.151-158
• Main Authors: Miura, Hiroto, Wachtel, Ruth E, Loberiza, Fausto R, Saito, Takashi, Miura, Mamoru, Nicolosi, Alfred C, Gutterman, David D
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Age Factors; Arterioles - drug effects; Arterioles - physiopathology; Associated diseases and complications; Biological and medical sciences; Bradykinin - pharmacology; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Diabetes Mellitus - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Glyburide - pharmacology; Humans; Hypoxia - physiopathology; In Vitro Techniques; Male; Medical sciences; Membrane Potentials - drug effects; Microcirculation - physiopathology; Middle Aged; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiopathology; Nitric Oxide Donors - pharmacology; Picolines - pharmacology; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels, Inwardly Rectifying - genetics; Potassium Channels, Inwardly Rectifying - metabolism; Pyrans - pharmacology; Risk Factors; RNA, Messenger - metabolism; Sex Factors; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - pharmacology
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.0000052671.53256.49

ABSTRACT—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