Effects of calcium channel blockers on coronary vasoconstriction induced by endothelin-1 in closed chest pigs.
The purpose of this study was to determine the effects of endothelin-1 on the coronary vascular bed of closed chest pigs. Endothelin-1 (3 to 30 pmol/kg body weight) was selectively administered into the left anterior descending coronary artery. Coronary blood flow and epicardial vessel diameter were measured by quantitative arteriography. Arterial pressure increased after a 30 pmol/kg dose and heart rate was not changed. Coronary blood flow and vessel diameter of the left anterior descending artery significantly decreased by 74% and 32%, respectively (p less than 0.01 versus control) after the 30 pmol/kg dose, whereas these variables modestly decreased in the left circumflex artery. Endothelin-1 in doses of 10 to 30 pmol/kg produced electrocardiographic ST segment elevation associated with decreased oxygen saturation of coronary sinus venous blood. Endothelin-induced coronary vasoconstriction was significantly inhibited after treatment with intravenous diltiazem (0.2 mg/kg, n = 6) or nifedipine (0.1 mg/kg, n = 5), but not after vehicle administration (n = 4). This study demonstrates that intracoronary administration of endothelin-1 causes significant myocardial ischemia through coronary vasoconstriction, which is inhibited by a calcium channel blocker. The data suggest that calcium influx into the smooth muscle cells appears to be involved at least in part in the mechanism of endothelin-induced coronary vasoconstriction in vivo.
Egashira
K
K
Charles A Dana Research Institute, Boston, Massachusetts.
Pipers
F S
FS
Rush
J E
JE
Morgan
J P
JP
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000209:etiology*; D003331:Coronary Vessels / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D016232:Endothelins; D004110:Diltiazem; D009543:Nifedipine