Effects of diazoxide on norepinephrine-induced vasocontraction and ischemic myocardium in rats.
Effects of diazoxide on norepinephrine-induced vasocontraction in vitro and global ischemia-induced lactate accumulation in the myocardial tissue in vivo were studied in rats. Diazoxide produced relaxation of the isolated rat aorta contracted by norepinephrine in a dose dependent manner. The relaxation of the aorta was associated with reduction of intracellular Ca2+ concentration. This reduction may be due either to activation of KATP channels or Na(+)-K+ ATPase, or to both. Global ischemia induced by aorta constriction for 30 min in vivo increased the myocardial tissue level of lactate. Pretreatment with diazoxide (10 mg.kg-1, i.v.) significantly attenuated the accumulation of lactate due to global ischemia. The present study suggests that diazoxide reduces ischemic influence on the myocardium partly through its vasodilatory action.
Nakai
T
T
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Ichihara
K
K
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003981:Diazoxide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D016257:Fura-2 / Q000737:chemistry; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D007773:Lactates; D014665:Vasodilator Agents; D019344:Lactic Acid; D010042:Ouabain; D003981:Diazoxide; D005905:Glyburide; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine