title: Characterization of intrinsic sympathomimetic activity of carteolol in rat cardiovascular preparations.
abstract: We evaluated in vitro, in myocardial and vascular preparations isolated from reserpine-treated rats, the intrinsic sympathomimetic activity (ISA) of carteolol, a beta(1)/beta(2)-adrenoceptor blocking agent used in cardiovascular and non-cardiovascular diseases. In spontaneously beating atria, carteolol, at low concentrations (0.01 and 0.1 microM), antagonized the positive inotropic effect of isoprenaline, whereas at higher concentrations (1 microM to 1 mM), it caused an increase in the force of contraction (EC(50): 4.6 +/- 0.1 microM, E(max): 17.1 +/- 1.1%, with respect to the maximum isoprenaline response) and a slight increase (7.8 +/- 1.9% over basal values) in the heart rate. The positive inotropic effect of carteolol was abolished by concentrations of propranolol or timolol (10 microM) much higher than those blocking isoprenaline effects in the same preparations. A similar positive inotropic effect was also observed in electrically driven left atrium and in Langendorff perfused hearts. Functional and biochemical evidences supported the involvement of cAMP in the cardiac action of carteolol. In peripheral arteries (femoral and tail) pre-contracted with phenylephrine, carteolol exerted ISA-related relaxing effects, independent of the presence of endothelium and sensitive to high concentrations (10 microM) of conventional beta-blockers. On the basis of these results, we propose to categorize carteolol as a non-conventional partial agonist of both cardiac and vascular beta-adrenoceptors.
authors.affiliation: Department of Pharmacology and Anaesthesiology, Pharmacology Section, University of Padova, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Floreani
authors.forename: Guglielmina
authors.initials: G
authors.lastname: Froldi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cavalli
authors.forename: Sergio
authors.initials: S
authors.lastname: Bova
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Giron
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Stefania
authors.initials: S
authors.lastname: Gessi
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dorigo
authors.forename: Paola
authors.initials: P
authors.lastname: Dorigo
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002354:Carteolol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D013566:Sympathomimetics; D002354:Carteolol