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Influence of the endothelium, nitric oxide and serotonergic receptors on coronary vasomotor responses evoked by ergonovine in conscious dogs
Author(s) -
KarilaCohen Daniel,
Delpy Eric,
DuboisRandé JeanLuc,
Puybasset Louis,
Hittinger Luc,
Giudicelli JeanFrançois,
Berdeaux Alain
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702635
Subject(s) - ergonovine , vasoconstriction , ketanserin , vasodilation , medicine , serotonergic , endothelium , cardiology , nitric oxide , endocrinology , coronary vasodilator , anesthesia , serotonin , receptor , 5 ht receptor , angina , myocardial infarction
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. In seven dogs with an endothelium intact, ergonovine (30–1000 μg, 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 μm, 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). After blockade of NO synthesis by N ω ‐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. 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. 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.British Journal of Pharmacology (1999) 127 , 1039–1047; doi: 10.1038/sj.bjp.0702635