Acetylcholine-induced coronary vasoconstriction and vasodilation in tranquilized baboons.
To determine the effects of acetylcholine on the coronary bed in the baboon and whether the effects preceded or followed the action of acetylcholine on ventricular function, eight adult baboons (Papio anubis) were instrumented to measure left ventricular (LV) and mean arterial pressures, LV dP/dt, regional myocardial function, and coronary blood flow. Acetylcholine was injected locally through a catheter positioned in the coronary artery ostium using fluoroscopic guidance in intact sedated baboons. With heart rate held constant, intracoronary acetylcholine (0.5 micrograms/kg) reduced coronary blood flow by 82 +/- 4% from a baseline value of 34 +/- 4 ml/min without a significant change in mean arterial pressure and with a reduction in LV dP/dt of only 12 +/- 3%. The decrease in coronary blood flow occurred before either LV dP/dt or regional myocardial function fell in the region of the heart receiving acetylcholine. After the intense coronary constriction, a later phase characterized by dilation was observed. The changes in coronary blood flow with acetylcholine were unaffected by combined alpha- and beta-adrenoceptor blockades but were abolished by muscarinic blockade. Low doses of acetylcholine elicited only coronary vasodilation. All doses of acetylcholine, administered directly into the iliac artery, also elicited only iliac vasodilation. Intracoronary acetylcholine in conscious dogs also induced only coronary vasodilation, whereas in conscious calves at higher doses, initial vasoconstrictor responses were observed, which also preceded reductions in regional myocardial function. These results suggest that the controversy surrounding the effects of acetylcholine can be reconciled on the basis of species, vascular bed studied, and dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Knight
D R
DR
Department of Medicine, Harvard Medical School, Boston, Mass.
Shen
Y T
YT
Young
M A
MA
Vatner
S F
SF
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010215:Papio; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D001285:Atropine; D011433:Propranolol; D000109:Acetylcholine; D010646:Phentolamine