title: Study of ridazolol on isolated canine and human coronary arteries.
abstract: Experiments were performed on isolated canine and human coronary arteries to study the alpha- and beta-adrenolytic properties of ridazolol. On canine coronary arteries precontracted with prostaglandin F2 alpha 2 microM and pretreated with phentolamine 1 microM, ridazolol competitively antagonized the isoproterenol-induced relaxations, with a pA2 value of 8.5 (7.8-9.1). Thereafter the alpha-adrenolytic activity of ridazolol was assessed on these same canine coronary vessels. Ridazolol activity was compared with that of prazosin on dose-response curves to norepinephrine in the presence of cocaine (30 microM) and propranolol (3 microM). Schild plots for both drugs gave straight lines, with slopes not different from unity. The pA2 value was 7.1 (6.8-7.3) for ridazolol and 8.1 (7.9-8.4) for prazosin. In another set of experiments the alpha-adrenolytic activity of ridazolol was compared on canine and human coronary arteries. A submaximal contraction with norepinephrine (10 microM) was first assessed in the presence of propranolol 3 microM. The addition of ridazolol 3 microM significantly decreased the norepinephrine (10 microM)-induced contractions of both preparations. However, the inhibition was more pronounced on canine coronary arteries. In conclusion, ridazolol is a potent beta-adrenergic antagonist with moderate alpha-adrenolytic activity. The weaker inhibition of the norepinephrine-induced contraction observed in human preparations suggests the presence of a heterogeneous population of postjunctional alpha adrenoceptors.
authors.affiliation: Cardiology Department, Erasmus Hospital, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Unger
authors.forename: G
authors.initials: G
authors.lastname: Berkenboom
authors.forename: J
authors.initials: J
authors.lastname: Fontaine
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011224:Prazosin; D011724:Pyridazines / Q000378:metabolism / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013045:Species Specificity
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011724:Pyridazines; D011943:Receptors, Adrenergic, beta; C055942:ridazolol; D009638:Norepinephrine; D011224:Prazosin