Effects of phenylephrine on intracellular Na+ and H+ activities in guinea-pig cardiac ventricular papillary muscles.

Abstract

Effects of phenylephrine (PE) on the contractility, intracellular Na+ activity (aNai), intracellular H+ activity (pHi), and membrane potential in guinea-pig cardiac ventricular papillary muscles were studied. In beating fibers, PE significantly increased the twitch offsion, pHi and the action potential duration but decreased aNai. These effects could be inhibited by phentolamine, but not by propranolol. In quiescent fibers, PE also increased the resting tension and pHi, and decreased aNai. Pretreatment with phentolamine completely abolished the effect of PE. Methylisobutyl amiloride (MIA), a potent inhibitor of Na(+)-H+ exchanger, significantly decreased membrane potential, aNai, and pHi without changing the resting tension. PE in the presence of MIA increased the resting tension and further decreased aNai without significant changes in membrane potential and pHi. Ouabain significantly decreased membrane potential and pHi, and increased the resting tension and aNai. In the ouabain-treated fiber, PE further increased the resting tension without decreasing aNai or increasing pHi. From these results, it appears that PE activates the Na(+)-K+ pump and Na(+)-H+ exchange through alpha-adrenoceptors. Activation of the Na(+)-K+ pump contributes, at least in part, to the enhanced Na(+)-H+ exchange. The increase in contractile force associated with a decrease in aNai is suggested to result from the intracellular alkalization and increased sensitivity of contractile protein to Ca2+.