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• W2061137068 abstract "Several new chemical entities (RP 52891, cromakalim and its derivatives) are potent and specific openers of vascular K+ channels. This mechanism is also shared, at least partially, by drugs such as minoxidil, diazoxide, pinacidil and nicorandil. The opening of plasmalemma K+ channels produces loss of cytosolic K+. This effect results in cellular hyperpolarization and functional vasorelaxation. In normotensive or hypertensive rats, K+ channel activators decrease aortic blood pressure (by producing a directly mediated fall in systemic vascular resistance) and reflexly increase heart rate. The former effect is not modified by specific blockers of classical vascular receptors but it is completely antagonized by the hypoglycemic sulphonylurea, glibenclamide, an established blocker of ATP-regulated K+ channels. K+ channel openers produce selective coronary vasodilatation and afford functional and biochemical protection to the ischemic myocardium. This salutary effect is mediated via cardiac K+ channel modulation and may result from an improved myocardial oxygen balance in the ischemic region. K+ channel openers increase plasma renin activity in animals as well as in man. However, only diazoxide, but not cromakalim or RP 52891, lowers plasma insulin concentration. The dose of glibenclamide entirely blocking the latter effect is over 50-fold smaller than that antagonizing the hypotensive and hyper-reninemic responses to diazoxide. In conclusion, K+ channel activators are potent vasorelaxant and cardioprotective agents possessing an original mechanism of action which is the opening of plasmalemma ATP-regulated K+ channels. Their clinical use as antihypertensive agents may be accompanied by undesirable effects (characteristic of peripheral vasodilators) which are likely to be attenuated or avoided by controlled release formulations. However, inasmuch as low doses of K+ channel openers may be sufficient to produce selective coronary artery dilatation and cardioprotection, these compounds could be of particular value in treating patients with coronary artery disease efficaciously and possibly without adverse cardiovascular effects." @default.
• W2061137068 created "2016-06-24" @default.
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• W2061137068 date "1990-01-01" @default.
• W2061137068 modified "2023-10-16" @default.
• W2061137068 title "Cardiovascular and biological effects of K+ channel openers, a class of drugs with vasorelaxant and cardioprotective properties" @default.
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• W2061137068 doi "https://doi.org/10.1016/0024-3205(90)90342-o" @default.
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