Cardiovascular effects of equinatoxin III from the sea anemone Actinia equina (L.)

Equinatoxin III is the most hemolytic, and the least lethal of the three ba sic proteins isolated from the sea anemone Actinia equina (L.). Its LD50 in mice is 83 mug/kg. Preliminary results on Wistar rats have suggested cardi orespiratory arrest as a putative cause of death, but the mechanism of its action has not yet been studied. So far only equinatoxin II has been invest igated more thoroughly. As equinatoxin II is less lythic, but more toxic, t han equinatoxin III (its LD50 in mice = 35 mug/kg), it may be assumed that haemolysis with a consequent rise in plasma potassium level is not the majo r factor in the lethality of equinatoxins. To assess the relative contribut ion of hyperkalemia in the lethality of the toxin in rat, the effects of eq uinatoxin III were compared to the effects of hyperkalemia caused by the in jection of KCl giving the same final concentration of K+ in the plasma as t hat observed after an i.v. injection of 3LD(50) of equinatoxin III. As coro nary vasoconstriction may be an important mechanism of the cardiotoxic acti on of equinatoxins, the effect of EqT III on isolated porcine coronary arte ries was studied by measurements of smooth muscle tension in the presence o f 1-100 nM equinatoxin III. The results revealed that animals survive the e levated K+ plasma concentration caused by an i.v. application of KCl. This suggests that equinatoxin III induced haemolysis is not the major mechanism of equinatoxin III lethality. However, equinatoxin III increases the potas sium induced contractions of coronary smooth muscle for 289 +/- 29%, sugges ting that coronary vasoconstriction may be an important factor in the cardi otoxic effects of equinatoxin III. (C) 2001 Elsevier Science Ltd. All right s reserved.