Characterization of intrinsic Sympathomimetic activity of Carteolol in Rat Cardiovascular preparations

We evaluated in vitro, in myocardial and vascular prepns. isolated from reserpine-treated rats, the intrinsic sympathomimetic activity (ISA) of carteolol, a β1/β2-adrenoceptor blocking agent used in cardiovascular and non-cardiovascular diseases. In spontaneously beating atria, carteolol, at low concns. (0.01 and 0.1 μM), antagonized the pos. inotropic effect of isoprenaline, whereas at higher concns. (1 μM to 1 mM), it caused an increase in the force of contraction (EC50: 4.6±0.1 μM, Emax: 17.1±1.1%, with respect to the max. isoprenaline response) and a slight increase (7.8±1.9% over basal values) in the heart rate. The pos. inotropic effect of carteolol was abolished by concns. of propranolol or timolol (10 μM) much higher than those blocking isoprenaline effects in the same prepns. A similar pos. inotropic effect was also obsd. in elec. driven left atrium and in Langendorff perfused hearts. Functional and biochem. 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 concns. (10 μM) of conventional β-blockers. On the basis of these results, we propose to categorize carteolol as a non-conventional partial agonist of both cardiac and vascular β-adrenoceptors.