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Comparison of responses to acetylcholine and serotonin on isolated canine and human coronary arteries

par Berkenboom, Guy ;Unger, Philippe ;Fang, Zhen Y.;Degré, Serge ;Fontaine, Jeanine
Référence Cardiovascular Research, 23, 9, page (780-787)
Publication Publié, 1989

Article révisé par les pairs

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Résumé :

Canine and human coronary arteries were studied in organ baths to compare the responses to acetylcholine and serotonin in the two species. The human coronary rings were isolated from seven patients without cardiac disease (mean age 15 years, range 7-20). In one set of experiments canine and human preparations were incubated with phentolamine, propranolol and ketanserin (all at 1 μmol·litre-1 concentration) and precontracted with prostaglandin F2α (PGF2α 1-2 μmol·litre-1). Acetylcholine (0.1-10 μmol·litre-1) and serotonin (0.1-100 μmol·litre-1) relaxed canine preparations dose dependently, the maximum responses (expressed as % of depression of PGF2α response) being 84 (SEM 6)% (n = 9) and 51(5)% (n = 6) respectively. In the same experimental conditions, acetylcholine and serotonin failed to relax the human coronary rings (n = 11) while substance P and bradykinin induced relaxations of 72(4)% (n = 11) and 66(7)% (n = 11) of PGF2α response respectively. In another set of experiments, dose-contraction curves were constructed for acetylcholine or serotonin (in presence of phentolamine and propranolol). On human rings with endothelium, methylene blue (10 μmol·litre-1), a non-specific inhibitor of endothelium derived relaxing factor (EDRF), potentiated these dose-contraction curves: markedly for serotonin, the EC50 decreasing from 1.2(0.2) to 0.22(0.08) μmol·litre-1 (n = 11, p<0.01) with a significant increase in the maximal response); and slightly for acetylcholine, EC50 decreasing from 0.84(0.11) to 0.40(0.13) μmol·litre-1 (n = 10, p<0.05) without significant change in the maximal response. On human rings without endothelium, methylene blue did not modify the dose-response curves either to acetylcholine (n = 7) or to serotonin (n = 7). Similar results were obtained on canine rings for the serotonin induced contractions.Thus on both canine and human coronary vessels the responses to acetylcholine and serotonin are influenced by endothelial function. However on human preparations, the acetylcholine induced contractions are much less modulated by this endothelial function than those induced by serotonin.