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.
Terzic
A
A
Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
Vogel
S M
SM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active; D006325:Heart Atria / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012964:Sodium / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D015221:Potassium Channels; D011942:Receptors, Adrenergic, alpha; D015222:Sodium Channels; D010656:Phenylephrine; D010042:Ouabain; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000584:Amiloride; D012964:Sodium