The inotropic effects of a synthetic pyrethroid decamethrin on isolated guinea pig atrial muscle

doi:10.1016/0014-2999(84)90279-6

European Journal of Pharmacology

Volume 98, Issues 3–4, 2 March 1984, Pages 313-322

https://doi.org/10.1016/0014-2999(84)90279-6 Get rights and content

Abstract

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 μM) increased the force of isometric contraction in a dose-dependent manner without affecting the resting tension. Propranolol (5 μM) reduced the magnitude of the pyrethroid's inotropic effect; however, a significant inotropic effect was still observed with 1 and 10 μM decamethrin in the presence of this concentration of propranolol. Similar results were noted in the presence of 500 μM 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.

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Three triazine herbicides, atrazine, simazine and metribuzine, and some of their major metabolites (cyanuric acid and 6-azauracil) were investigated for their action on synaptic terminals using three different isolated tissue preparations from the atria of the frog, Rana ridibunda, the heart of the honeybee, Apis mellifera macedonica, and the ventral nerve cord of the beetle, Tenebrio molitor. The results indicate that triazines facilitate the release of neurotransmitters from nerve terminals, as already reported for the mammalian central nervous system. The no observed effect concentration, the maximum concentration of the herbicide diluted in the saline that has no effect on the physiological properties of the isolated tissue, was estimated for each individual preparation. According to their relative potency, the three triazines tested can be ranked as follows: atrazine (cyanuric acid), simazine>metribuzine (6-azauracil). The action of these compounds on the cholinergic (amphibians, insects), adrenergic (amphibian) and octopaminergic (insects) synaptic terminals is discussed.
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The inotropic effects of a synthetic pyrethroid decamethrin on isolated guinea pig atrial muscle

Abstract

Pestic. Biochem. Physiol.

Arch. Biochem. Biophys.

Pest. Biochem. Physiol.

Gen. Pharmacol.

Pest. Biochem. Physiol.

J. Biol. Chem.

Biochem. Pharmacol.

Biochim. Biophys. Acta

European J. Pharmacol.

European J. Pharmacol.

Gen. Pharmacol.

European J. Pharmacol.

Cardiovascular toxicology of cardiotonic drugs and chemicals

Effects of grayanotoxin I on cardiac Na+,K+-adenosine triphosphatase activity, transmembrane potential and myocardial contractile force

J. Pharmacol. Exp. Ther.

The complexes of ouabain with sodium- and potassium-activated adenosine triphosphatase formed with various ligands: Relationship to the complex formed in the bearing heart

Mol. Pharmacol.

Characterization of batrachotoxin-induced depolarization of the squid giant axons

J. Pharmacol. Exp. Ther.

Calcium transients in aequorin-injected frog cardiac muscle

Nature

Effects of grayanotoxin I on cardiac Na⁺,K⁺-adenosine triphosphatase activity, transmembrane potential and myocardial contractile force