Nicardipine and tezosentan modulate calcium dependent vasoconstrictory effectsof equinatoxin II on isolated rat heart = Nikardipin in tenzosetan modulirata od kalcija odvisne vazokonstriktorne učinke na izoliranem srcu podgane
Bunc, Matjaž ; Šuput, Dušan ; Drevenšek, Gorazd
Equinatoxin II (EqT II) is one of three isotoxins isolated from the sea anemone Actinia equina (L.). The main cause of toxin lethality after i.v. application are cardio-respiratory effects. The ...precise mechanism of the cardiotoxic effects of the toxin is unknown. The importance of nicardipine, aspirin, tezosentan and different concentrations of CaCl2 in a perfusion solution on lowering the coronary flow of isolated rat hearts due to EqT II application were investigated. On a Langendorff rat heart an EqT II preparation caused a dose dependent lowering of coronary flow. A bolus of 1 mlof 10 nM EqT II (0.6 0.1 mM/100g of rat heart) caused the maximum drop in coronary flow to 7.8 % 4.1 of the control value. At concentrations of the toxin lower than 1 nM no changes of coronary flow could be detected. Lowering of the coronary flow depended upon the Caz' concentration in the perfusion solution. The strongest effect of 10 nM of the toxin was observed when hearts were perfused with 1.5 mM CaCl2. The coronary flow decreased to 7.8% 4.1 of the control value. On the other hand, EqT I I did not affect the coronary flowwhen applied in a K-H solution containing 0 mM CaCl2. Nicardipine diminished the EqT II effect on coronary flow in a concentration dependent manner. The effect was maximum at a 0.1 mM concentration, when it lowered the effect of EqT II by 18% 6, but at concentrations lower than 1 nM it had no effect on the toxin action. Aspirin had only a negligible effect on the actionof EqT II on coronary flow. 1 mM tezosentan diminished the lowering of coronary flow by EqT II by about 20%. The results give the conclusion that calcium ions, L-type calcium channels and endothelin receptors are involved inthe lowering of coronary flow produced by EqT II.
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