Phosphodiesterases inhibition unmask a positive inotropic effect mediated by β2-adrenoceptors in rat ventricular myocardium

The effects of salbutamol on contractility and cAMP levels were investigated in rat right ventricular myocardium. Salbutamol (1–300 μM), produced a concentration-dependent positive inotropic effect which was not affected by ICI 118551 (50 nM), a β2-adrenoceptor antagonist but was abolished by CGP 20712A (1 μM) a β1-adrenoceptor antagonist. However, in rats pretreated with pertussis toxin (30 μg/kg intraperitoneal injection) salbutamol increases contractility (Emax = 9.8 ± 1.8%, − log EC50 = 6.25 ± 0.07, n = 5). The combination of salbutamol + CGP 20712A, also produces a concentration-dependent enhancement of contractility (Emax = 43.0 ± 7.5%, − log EC50 = 6.3 ± 0.04, n = 6), in the presence of 30 μM of the non selective phosphodiesterase (PDE) inhibitor 3-isobutylmethylxantine (IBMX) which was prevented by ICI 118551 (50 nM). Also, salbutamol + CGP 20712A fail to increase cAMP tissue levels but enhance them in the presence of IBMX. This effect was also prevented by ICI 118551. These results indicate that PDEs blunt contractility and cAMP production mediated by β2-adrenoceptors in rat ventricular myocardium. Gi protein, although less efficiently than PDEs, also limits inotropic effects of salbutamol mediated by β2-adrenoceptors in this tissue.