title: The positive inotropic action of triamterene in isolated heart tissues. Its interaction with beta-adrenergic agonists and electrophysiological investigations.
abstract: Triamterene (20--80 mumol/l) inhibits the positive inotropic action of orciprenaline in guinea-pig left atria. 200 mumol/l triamterene completely suppress the effect of orciprenaline (10(-8)--10(-4) mol/l). But if orciprenaline is applied first and triamterene afterwards no antagonism can be seen; triamterene shows an additional positive inotropic effect. A mathematical model is presented which allows a quantitative description of the interaction if two different sites of action are accepted for triamterene: a stimulating effect mediated via inhibition of phosphodiesterase and leading to an increase in slow inward current and an inhibition of the orciprenaline-adenylcyclase complex. The additional increase in contractile force by triamterene after pretreatment with orciprenaline can be explained by the model if the blocking site of triamterene is not considered. Triamterene increases force of isometric contraction and broadens action potential in all repolarization phases in guinea-pig left atria to a greater extent than in papillary muscles. 100 mumol/l triamterene increases action potential duration at 30% repolarization in atria by 109 +/- 13% (n = 4) and in papillary muscles by 28 +/- 4% (n = 4). These effects also occur to a similar degree when the animals have been pretreated with reserpine 2 mg/kg on 2 days prior to the experiment. Maximum upstroke velocity of atrial and ventricular action potentials is not changed up to 100 mumol/l triamterene, indicating its lack of influence on cardiac fast sodium channels.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D004594:Electrophysiology; D006168:Guinea Pigs; D008297:Male; D009921:Metaproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D014223:Triamterene / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D009921:Metaproterenol; D012110:Reserpine; D014223:Triamterene