Characterization of intrinsic sympathomimetic activity of carteolol in rat cardiovascular preparations.
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.
Floreani
Maura
M
Department of Pharmacology and Anaesthesiology, Pharmacology Section, University of Padova, Italy.
Froldi
Guglielmina
G
Cavalli
Maurizio
M
Bova
Sergio
S
Giron
Maria Cecilia
MC
Varani
Katia
K
Gessi
Stefania
S
Borea
Pier Andrea
PA
Dorigo
Maria Teresa
MT
Dorigo
Paola
P
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*
D002316:Cardiotonic Agents; D013566:Sympathomimetics; D002354:Carteolol