Amiloride-sensitive actions of an alpha-adrenoceptor agonist and ouabain in rat atria.

The influence of amiloride, a known blocker of Na/H exchange, on the positive inotropic action of alpha-adrenoceptor stimulation was investigated in isolated rat left atria. Amiloride (300 microM) rapidly (within 10 min) and reversibly abolished the positive inotropic effect of phenylephrine (10 microM; 3 microM propranolol present). Lower concentrations of amiloride inhibited the increase in contractile force caused by phenylephrine in a concentration dependent manner (IC50 of 50 microM). At a concentration of 50 microM, amiloride caused a rightward and downward shift in the concentration-response curve to phenylephrine. Amiloride (10 to 300 microM) affected to only a small extent the increased contractile force in the presence of inotropic interventions known to increase Ca2+ influx via L-type calcium channels (Bay K 8644) and the Na/Ca exchanger (reduced extracellular Na+). To provide evidence that amiloride inhibits the Na/H antiporter intact atria, a contracture that depends on Na+ influx by the Na/H antiporter was examined. Amiloride fully relaxed the contracture induced by ouabain (1 mM) or potassium-free solutions in the identical concentration range over which amiloride inhibited the positive inotropic effect of phenylephrine. Phenylephrine increased the rate of development and the peak amplitude of the amiloride-sensitive contracture (ouabain-induced). The inhibitory action of amiloride on the positive inotropic response to phenylephrine may, in part, be the result of inhibition of the Na/H antiporter.