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Functional roles of calcium-activated potassium channels on the mechanical activity of epicardial coronary arteries obtained from a canine model of diabetes were investigated. Coronary arteries were isolated from healthy, alloxan-diabetic and insulin-treated diabetic dogs. Basal tensions, contractions induced by the prostaglandin (PG) analogue, U46619, and endothelium-dependent relaxations to acetylcholine (ACh) were modified with charybdotoxin (CHTX) + apamin (APA), inhibitors of calcium-activated potassium channels, as well as with N(omega)-nitro-l-arginine (LNA) + indomethacin (INDO) to suppress the synthesis of nitric oxide (NO) and PGs. The relaxing effect of nitroprusside-sodium (SNP), an NO donor, was also determined. In diabetic coronary arteries, CHTX + APA did not change while LNA + INDO elevated the basal tension. PG-induced contractions were enhanced by CHTX + APA and by LNA + INDO in all the three groups of animals. CHTX + APA decreased the maximal relaxations to ACh in a partly insulin-dependent manner. LNA + INDO abolished the endothelium-dependent relaxations to ACh. In diabetic coronary arteries, the sensitivity to SNP-induced relaxation was enhanced, insulin independently, suggesting that NO could be partly responsible for maintaining intact ACh-induced vasorelaxation. In diabetic canine coronary artery, the vasomotor responses reflect up-regulation of calcium-activated potassium channels. This endothelial mechanism of the canine epicardial coronary artery may oppose vasoconstrictions in diabetic vascular tissue.

Citation

J Pataricza, Z Márton, Cs Lengyel, M Tóth, J Gy Papp, A Varró, A Kun. Potassium channels sensitive to combination of charybdotoxin and apamin regulate the tone of diabetic isolated canine coronary arteries. Acta physiologica (Oxford, England). 2008 Sep;194(1):35-43

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PMID: 18394024

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