The inotropic effects of a synthetic pyrethroid decamethrin on isolated guinea pig atrial muscle.
Pyrethroid insecticides have been reported to increase transmembrane sodium influx and inhibit ion-dependent ATPases in insect, squid, and toad nerve tissues. Since changes in sarcolemmal ion fluxes and inhibition of membrane-bound ATPases can alter myocardial contractility, the effects of a potent synthetic pyrethroid, decamethrin, on mammalian myocardium were examined using isolated left atrial muscle of the guinea-pig heart electrically stimulated at 1.5 Hz. Decamethrin (0.1-10 microM) increased the force of isometric contraction in a dose-dependent manner without affecting the resting tension. Propranolol (5 microM) reduced the magnitude of the pyrethroid's inotropic effect; however, a significant inotropic effect was still observed with 1 and 10 microM decamethrin in the presence of this concentration of propranolol. Similar results were noted in the presence of 500 microM procainamide and in left atrial muscle obtained from reserpine-treated animals. The results suggest that decamethrin increased the force of myocardial contraction by two mechanisms; indirectly by releasing catecholamines from sympathetic nerve terminals and directly by an action on the myocardium. Inotropic concentrations of the pyrethroid did not inhibit partially purified rat brain or guinea pig heart Na+, K+-ATPase. Moreover, twitch tension recordings of isometric contractions showed that, in the presence of propranolol, decamethrin increased tension development without changing either the time to peak tension or the duration of contraction. Tetrodotoxin almost completely abolished the positive inotropic effect of decamethrin. Thus, the positive inotropic effect of decamethrin is apparently due to an increase in transmembrane sodium influx which causes catecholamine release from the sympathetic nerve terminals and also directly enhances muscle contraction.
D000818:Animals; D016275:Atrial Function; D002395:Catecholamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009570:Nitriles; D011433:Propranolol / Q000494:pharmacology; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology
D002395:Catecholamines; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; D013779:Tetrodotoxin; D011433:Propranolol; D000254:Sodium-Potassium-Exchanging ATPase