ERGOMETRINE CONTRACTS ISOLATED CANINE CORONARY-ARTERIES BY A SEROTONERGIC MECHANISM - NO ROLE FOR ALPHA-ADRENOCEPTORS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 218  (2) , 530-536
Abstract
Studies were performed on isolated canine coronary artery segments to characterize the mechanism of the constrictor response of ergometrine (ergonovine), an agent used to induce coronary vasospasm in patients with variant angina. Changes in isometric tension were measured in coronary ring segments suspended in organ baths at 37.degree. C filled with a buffered salt solution. Single concentration-response curves were obtained in each tissue by cumulative addition of agonist. Maximum responses to 5-hydroxytryptamine (5-HT) were greater than for ergometrine or phenylephrine but ergometrine had the lowest EC50 [median effective concentration]. .alpha. adrenoceptor block by prazosin (10 nM) or the irreversible antagonist benextramine tetrahydrochloride did not affect responses to 5-HT or ergometrine. Cyproheptadine and pizotifen (0.1-1 .mu.M) depressed the ergometrine and 5-HT concentration-response curves with no change in the location of the EC50 values. Methysergide (0.01-1 .mu.M) had concentration-dependent constrictor activity which was noncompetitively antagonized by cyproheptadine, but unaltered by benextramine tetrahydrochloride pretreatment. Methysergide also competitively antagonized the 5-HT and ergometrine concentration-response curves. Estimates of methysergide pKB values (-log dissociation constant) from computer analysis were 7.9 and 8.0 for the 2 agonists, respectively. Methysergide is a partial 5-HT agonist but cyproheptadine and pizotifen are noncompetitive 5-HT antagonists. Ergometrine is a potent 5-HT receptor agonist in canine coronary artery with negligible .alpha.-adrenoceptor agonist activity.