Abstract

Epicardial coronary artery strips of cattle hearts mounted in vitro respond to transmural stimulation with a neurogenic constriction, attributable to the endogenous release of acetylcholine. These responses were elicited with frequencies as low as 1.0 Hz and with pulse durations as low as 100 microseconds. The magnitude of the contractile response increased with increasing frequency of stimulation. Blockade of adrenergic neuronal mechanisms with guanethidine (5 x 10(-6) M) increased the size of the contractile responses at 10 Hz and they were antagonized markedly by the muscarinic antagonist atropine (4.3 or 8.6 x 10(-7) M), but not by the adrenergic antagonist phentolamine (3.6 x 10(-7) M). Contractions to field stimulation were increased greatly by the cholinesterase inhibitor physostigmine (1.1 x 10(-6) M). Blockade of neuronal sodium channels with tetrodotoxin (9.4 x 10(-7) M) reduced severely the contractions to field stimulation, as did cold storage of coronary vessels for 5 or 6 days. The contractile responses to stimulation were not inhibited significantly by antagonists of prostaglandin synthesis, or were they enhanced by denudation of the endothelium. It is concluded that cholinergic constrictor mechanisms, linked to medial muscarinic receptors, operate in the large coronary arteries, which are associated in humans with coronary spasm.