Author/Editor		Bunc, Matjaž; Šuput, Dušan; Drevenšek, Gorazd
Title		Nicardipine and tezosentan modulate calcium dependent vasoconstrictory effects of equinatoxin II on isolated rat heart
Translated title		Nikardipin in tenzosetan modulirata od kalcija odvisne vazokonstriktorne učinke na izoliranem srcu podgane
Type		članek
Source		Slov Kardiol
Vol. and No.		Letnik 2, št. 1
Publication year		2005
Volume		str. 2-7
Language		eng
Abstract		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 ml of 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 flow when 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 action of 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 in the lowering of coronary flow produced by EqT II.
Summary		Ekvinatoksin II (EqT II) je eden izmed treh izotoksinov izoliranih iz morske vetrnice Actinia equine (L.). Glavni vzrok letalnosti toksina so kardiorespiratorni učinki toksina. Mehanizmi kardiotoksičnosti niso poznani. Testirani so bili vplivi nikardipina, aspirina, tezosentana ter različnih koncentracij CaCL2 na zmanjšanje koronarnega pretoka na izoliranih podganjih srcih po dodatku EqT II. Na izoliranih podganjih srcih tretiranih po Langendorffovi metodi je EqT II povzročil od odmerka odvisno znižanje koronarnega pretoka. Bolus 1 ml 10 nM EqT II (0.6± 0.1 mM/100g podganjega srca) je povzročil znižanje koronarnega pretoka na 7.8 %± 4.1 kontrolne vrednosti. Aplikacija toksina v odmerkih nižjih od 1 nM ni povzročila merljivih sprememb koronarnega pretoka izoliranih podganjih src. Učinek toksina na koronarni pretok je bil odvisen od koncentracije kalcijevih ionov v perfuzijski raztopini. Največji je bil učinek 10 nM toksina, ko je bila koncentracija kalcija v perfuzijski raztopini 1.5 mM CaCl2, ko se je pretok znižal na 7.8% ± 4.1. V primeru, ko v perfuzijski raztopini ni bito kalcijevih ionov, pa EqT II ni povzročil merljivih sprememb koronarnega pretoka na izoliranih podganjih srcih. Zaviralec kalcijevih kanalčkov tipa L nikardipin je povzročil od koncentracije odvisno zmanjšanje učinkov EqT II na koronarni pretok. Največji je bil učinek 0.1 mM nikardipina, ki je zmanjšal učinek EqT II na koronarni pretok za 18%± 6, pri koncentraciji nikardipina pod 1 nM pa opisanega vpliva nicardipina ni bilo opaziti. Aspirin je imel le zanemarljive učinke na EqT II toksičnost. Tezosentan je zmanjšal učinek EqT II na koronarni pretok za cca 20%. Dobljeni rezultati dokazujejo, da so kalcijevi kanalčki tipa L ter endotelinski receptorji vpleteni v mehanizem zmanjšanja koronarnega pretoka na izoliranih podganjih srcih po dodatku EqT II.
Descriptors		CORONARY CIRCULATION HEART CNIDARIAN VENOMS ASPIRIN CALCIUM RATS, WISTAR RECEPTORS, ENDOTHELIN SEA ANEMONES DOSE-RESPONSE RELATIONSHIP, DRUG