Effect of ethacrynic acid on spontaneous contractions of isolated guinea-pig atria

Pousti, Abbas; Zarrindast, M.R.; Sadeghi, Dj.; Khoyi, M. A.

doi:10.1016/0014-2999(73)90037-x

Cited by 5 publications

(7 citation statements)

References 2 publications

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“…It is clear from the data presented that ethacrynic acid does have a positive inotropic effect upon cardiac muscle and subsequent to our preliminary report (4), these observations have been confirmed (5,6).…”

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confidence: 83%

Ethacrynic Acid Induced Inotropism

From

Probstfield

Smith

1975

Experimental Biology and Medicine

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Ethacrynic acid (ECA) is frequently administered in the presence of acute pulmonary edema. The major mechanisms of improvement in such patients are thought to be an acute reduction of blood volume stemming from the diuresis induced by the drug and drug-induced vasodilation (1, 2). Until recently there has been little direct exploration of the possibility that ECA might also have a direct cardiac effect (3-6). Our own previous work with N-ethyl maleimide (NEM) (7) and P-chloromercuribenzene sulfonic acid (PCMBS) (8), two classical sulfhydryl group inhibitors demonstrated they had positive inotropic properties. Because of the striking hemodynamic response frequently following the administration of ECA and because the compound is known to act by inhibiting sulfhydryl groups (9), ECA was evaluated for possible positive inotropic properties.Methods. Isolated guinea pig left atria were placed in a tissue bath and isometric tension was measured with a strain gauge transducer (Statham, UC3) and recorded with an oscillographic recording system (Sanborn 35 1). Tyrode's solution containing 4 mM K and either 1.8 mM or 0.9 mM Ca was utilized as the bath medium and was bubbled with a 95% O2 and 5% C02 mixture which maintained the pH at approximately 7.3. The bath temperature was maintained at 37". The muscles were paced at 160 beats/min at a voltage 10% above the threshold, utilizing large platinum field electrodes. The preload (diastolic tension) was set at approximately 300 mg in each experiment.Drug solutions were made up daily.

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supporting

confidence: 83%

Ethacrynic Acid Induced Inotropism

From

Probstfield

Smith

1975

Experimental Biology and Medicine

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“…Long term treatment (7 to 8 days) of rats with EA depletes heart muscle of catecholamine, but does not change the noradrenaline (NA) concentration in kidneys, adrenal glands, epididymal fat tissue and brain (Torsti, Vapaatalo & Neuvonen, 1968). A previous report from this laboratory suggested that EA releases catecholamines from guinea-pig isolated atria (Pousti, Zarrindast, Sadeghi & Khoyi, 1973).…”

Section: Introductionmentioning

confidence: 88%

The Effect of Ethacrynic Acid on the Guinea‐pig and Rat Isolated Vas Deferens

Khoyi

Pousti

Zarrindast

1974

British J Pharmacology

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The effect of ethacrynic acid (EA) was studied on guinea-pig and rat vas deferens in vitro. 2 EA contracted the guinea-pig but not the rat vas deferens in a dose-dependent manner (50-800,ug/ml). Tyramine caused contraction in 10 out of 18 guinea-pig vas deferens; EA caused contraction in 17 of the preparations which did not respond to tyramine. Repeated doses of EA produced tachyphylaxis, but there was no cross tachyphylaxis to tyramine. 3 The contractions produced by EA were prevented by phentolamine or reserpine pretreatment and potentiated by cocaine. A low concentration of desipramine (3 ng/ml) potentiated and higher concentrations (0.6 and 3.0 Ag/ml) inhibited the response of vas deferens to EA.4 Hexamethonium (100lg/ml) or atropine (0.1 lg/ml) did not inhibit the effect of EA, excluding the nicotinic and muscarinic receptors as the sites of action. 5 The effect of noradrenaline (NA) on the guinea-pig and rat vas deferens was enhanced by EA pretreatment, which may be due to inhibition of NA uptake. 6 It is concluded that EA releases NA from guinea-pig vas deferens. The mechanism of release seems to be different from that of tyramine.

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“…In previous reports (Pousti, Zarrindast, Sadeghi & Khoyi, 1973;Khoyi, Pousti & Zarrindast, 1974) we have shown that ethacrynic acid increases the force and rate of contraction of spontaneously beating isolated atria and contracts the vas deferens of the guinea-pig. The cardiac effects are blocked by propranolol or reserpine pretreatment whilst the effects on the vas deferens are prevented by phentolamine or reserpine pretreatment and are potentiated by cocaine and low concentrations of desipramine.…”

Section: Introductionmentioning

confidence: 80%

“…The method of preparation and recording from the isolated atrium was as described previously (Pousti et al, 1973), except that left atria were used to study alterations in the amplitude of contractions and right or whole atria were used to study the changes in the rate of contractions. The isolated atria were suspended in a bath containing 20 ml of oxygenated Ringer Locke solution, pH 7.4, (37°C) of the following composition (mM): NaCl 158.8, KCI 5.6, CaCl2 2.16, NaHCO3 5.9 and glucose 5.5.…”

Section: Methodsmentioning

confidence: 99%

Tachyphylaxis to Ethacrynic Acid in the Isolated Atrium of Guinea‐pig and Its Relation to Noradrenaline Stores

Khoyi¹,

Pousti

Powis³

et al. 1978

British J Pharmacology

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The isolated electrically‐paced atrium of the guinea‐pig developed a dose‐dependent increase in the force of contraction in response to ethacrynic acid (12–100 μg/ml) which was blocked by pretreatment of the animals with reserpine but was unaffected by desipramine or colchicine added to the bathing medium. There was a rapidly developing tachyphylaxis to repeated doses of ethacrynic acid which was not reversed by rest or incubation of the tissue with noradrenaline. There was no cross tachyphylaxis between ethacrynic acid and tyramine, amphetamine or nicotine. Ethacrynic acid (200 μg/ml) decreased the noradrenaline content of the atria by 32%. It is concluded that ethacrynic acid exerts its effects indirectly through the release of endogenous noradrenaline and that the mechanism of release seems to be different from that of other known indirect sympathomimetic drugs.

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Effect of ethacrynic acid on spontaneous contractions of isolated guinea-pig atria

Cited by 5 publications

References 2 publications

Ethacrynic Acid Induced Inotropism

Ethacrynic Acid Induced Inotropism

The Effect of Ethacrynic Acid on the Guinea‐pig and Rat Isolated Vas Deferens

Tachyphylaxis to Ethacrynic Acid in the Isolated Atrium of Guinea‐pig and Its Relation to Noradrenaline Stores

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