Characterization of intrinsic sympathomimetic activity of carteolol in rat cardiovascular preparations

J Pharmacol Sci. 2004 May;95(1):115-23. doi: 10.1254/jphs.95.115.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology
  • Carteolol / pharmacology*
  • Dose-Response Relationship, Drug
  • Heart Atria / drug effects
  • In Vitro Techniques
  • Male
  • Myocardial Contraction / drug effects*
  • Myocardial Contraction / physiology
  • Rats
  • Rats, Wistar
  • Sympathomimetics / pharmacology*

Substances

  • Cardiotonic Agents
  • Sympathomimetics
  • Carteolol