Effects of diazoxide on KCl- and norepinephrine-induced contraction in isolated rat aorta.
Diazoxide produced endothelium-independent relaxations of the rat aorta contracted by either low concentrations of KCl or norepinephrine (NE). However, contraction with a high concentration of KCl was not altered by diazoxide. Hydrochlorothiazide did not affect the contraction induced by either KCI or NE. Tetraethylammonium and glibenclamide inhibited the relaxations of the aorta induced by diazoxide. Diazoxide significantly reduced the phasic and tonic contractions under Ca2+-free conditions induced by NE and CaCl2 following NE addition, respectively. These results suggest that diazoxide dilates vascular smooth muscle by opening the ATP-sensitive K+ channels and inhibiting receptor-operated Ca2+ movements from either the intracellular store sites or extracellular space to the cytoplasm, but not antagonizing voltage-dependent Ca2+ channels directly.
Nakai
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Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D003981:Diazoxide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D011189:Potassium Chloride; D003981:Diazoxide; D005905:Glyburide; D009638:Norepinephrine