The positive inotropic effect of phenylephrine in the presence of propranolol. Increase in time to peak force and in relaxation time without increase in c-AMP

Abstract

The effects of phenylephrine on the shape of the contraction curve and on the cyclic adenosine 3',5'-monophosphate (c-AMP) content were studied in electrically driven (frequency 0.2 Hz) cat papillary muscles. All experiments were done in the presence of 1 micron propranolol in order to minimize interference from beta-adrenoceptors. 1. Phenylephrine increased the force of contraction in a concentration-dependent manner. Maximal effects (about 200% of control) occurred at 30 micron phenylephrine. 2. The positive inotropic effect (PIE) of phenylephrine was antagonized by phentolamine. Phentolamine, 5 micron, produced a parallel shift of the concentration-response curve for the PIE of phenylephrine by about two log units to the right. 3. The PIE of 30 micron phenylephrine occurred without any detectable increase in the c-AMP levels of the preparations. 4. The PIE of 30 micron phenylephrine developed about three times more slowly than the PIE of an equieffective concentration of isoprenaline. 5. The PIE of phenylephrine was accompanied by significant, concentration-dependent increases in both time to peak force and relaxation time. 6. It is concluded that the PIE of phenylephrine in the presence of propranolol is mediated mainly by a stimulation of alpha-adrenoceptors. It is unlikely to be related to an increase in c-AMP. With respect to time course and influence on the shape of the contraction curve it is qualitatively different from the effects of beta-adrenoceptor stimulation. These data are taken to support the hypothesis that the mechanical effects of alpha- and beta-adrenoceptor stimulating agents on the heart are produced by different mechanisms.