Mechanical and ionic response of rat aorta to diazoxide.
Diazoxide provoked concentration-dependent and endothelium-independent relaxations of the mechanical responses evoked by low concentrations of KCl. Glibenclamide, tolbutamide and tetraethylammonium shifted the concentration-response curve for diazoxide to the right. The drug also caused a dose-dependent stimulation of 86Rb outflow which was inhibited by glibenclamide and tolbutamide. Diazoxide (10(-4) and 10(-3) M) inhibited the contractions elicited by 10(-1) M K+ and provoked a concentration-dependent reduction in the contractile responses to Ca2+. Diazoxide also reduced the KCl (8 x 10(-2) M)-induced increase in 45Ca outflow. These data indicate that the vasorelaxant properties of diazoxide are probably related to an inhibition of Ca2+ entry into smooth muscle cells. The reduction in Ca2+ entry appears to result from K+ channel activation. At high concentrations, diazoxide also exhibited antagonistic actions on voltage-sensitive Ca2+ channels.
Antoine
M H
MH
Laboratory of Pharmacology, Brussels Free University, Faculty of Medicine and Pharmacy, Belgium.
Berkenboom
G
G
Fang
Z Y
ZY
Fontaine
J
J
Herchuelz
A
A
Lebrun
P
P
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D002132:Calcium Radioisotopes; D003981:Diazoxide / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D007003:Hypoglycemia / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D002132:Calcium Radioisotopes; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D013453:Sulfonylurea Compounds; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D011189:Potassium Chloride; D003981:Diazoxide; D002118:Calcium