Influence of the endothelium, nitric oxide and serotonergic receptors on coronary vasomotor responses evoked by ergonovine in conscious dogs

1 The respective contributions of coronary Vascular endothelium, nitric oxide (NO) and serotonergic receptors to the effects of ergonovine on large and small coronary arteries were investigated in conscious dogs. 2 In seven dogs with an endothelium intact, ergonovine (30-1000 mu g, i.v.) induced a biphasic response on large coronary artery with an early and transient vasodilatation (up to +2.9 +/- 0.5% from 3310 +/- 160 mu m, P < 0.01) followed by a sustained vasoconstriction (down to -4.9 +/- 0.5%, P < 0.001) which occurred simultaneously with a sustained increase in coronary blood flow (CBF) (up to +100 +/- 26% from 28 +/- 4 ml min(-1), P < 0.001). After endothelium removal (balloon angioplasty), the ergonovine-induced vasodilatation was abolished and vasoconstriction potentiated (-6.4 +/- 0.9% after vs -4.9 +/- 0.5% before endothelium removal, P < 0.01). 3 After blockade of NO synthesis by N-omega-nitro-L-arginine (30 mg kg(-1)) in four other dogs, the early vasodilatation induced by ergonovine was abolished but the delayed vasoconstriction as well as the increase in CBF remained unchanged. 4 Both ketanserin and methiothepin (0.3 mg kg(-1)) abolished the early vasodilatation and reduced the delayed vasoconstriction induced by ergonovine. Ketanserin decreased and methiothepin abolished the reduction in coronary resistance induced by ergonovine. 5 Thus, the complex interactions between vascular endothelium and serotonergic receptors to ergonovine-induced constriction of large coronary arteries might explain the induction of coronary spasms in patients with endothelial dysfunction.