Cardiac effects of acetylcholine in rat hearts: role of endothelium-derived relaxing factor and prostaglandins.
We examined the effects of acetylcholine (ACh) on coronary perfusion pressure (CPP) and force of cardiac contraction (FCC) in isolated rat hearts. Perfusion of hearts with ACh increased both CPP and the FCC, whereas cardiac contraction rate fell. These effects of ACh were abolished by atropine but were not affected by the beta 1-adrenergic antagonist metoprolol. The nonselective beta-adrenergic antagonist propranolol decreased ACh-mediated increase in FCC but did not affect the rise in CPP. Pretreatment of hearts with cyclooxygenase inhibitor indomethacin or thromboxane (Tx) A2-endoperoxide receptor antagonist SQ 29,548 decreased ACh-mediated increase in CPP and FCC, suggesting release of TxA2 in the microvasculature, which may partially account for the increase in CPP and FCC with ACh infusion. In contrast to the effect of indomethacin and SQ 29,548, pretreatment of hearts with endothelium-derived relaxing factor (EDRF) synthetase inhibitor NG-monomethyl-L-arginine (L-NMMA) or guanylate cyclase inhibitor methylene blue potentiated ACh-mediated increase in CPP and attenuated the increase in FCC, suggesting that ACh-mediated increase in CPP is modified by basal EDRF release. Thus the cardiac effects of ACh are related to muscarinic receptor activation, and the release of prostaglandins and EDRF modulates the effects of ACh in isolated rat heart.
Yang
B C
BC
Department of Medicine, University of Florida College of Medicine, Gainesville.
Nichols
W W
WW
Mehta
J L
JL
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D011464:Epoprostenol / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D000109:Acetylcholine