Tezosentan inhibits both equinatoxin II and endotelin-1 induced contractions of isolated porcine coronary artery in a similar way.
In the present study we examined the endothelium-dependent mechanism in the constriction of the isolated porcine coronary artery induced by Equinatoxin II (EqT II). EqT II is a polypeptide isolated from the sea anemone (Actinia equina, L.). Contractions induced by endothelin-1 (ET-1) were compared with the contractions induced by EqT II. The force of contraction induced by 100 nM EqT II reached only 30% of the force of contraction induced by 100 nM ET-1. EC50 for ET-1 was 5.14 nM, and for EqT II 101.1 nM. The effects of tezosentan, an endothelin ETA/B receptor antagonist, on contractions induced by either ET-1 or EqT II were compared. Tezosentan inhibited both ET-1 and, to a lesser extent, EqT II-induced contractions of isolated porcine coronary artery. Our present results confirm the involvement of endothelium in the EqT II-induced contractions of coronary arteries. The mode of action of tezosentan upon EqT II-induced contractions indicate that besides its pore-forming effect in the membranes, endothelium, and specifically endothelin-dependent mechanisms, are very important components of the toxin constrictory effects.
Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Slovenia. gorazd.drevensek@mf.uni-lj.si
Gorazd
G
Drevensek
Simona
S
Kirbis
Matjaz
M
Bunc
Mojca
M
Zitko
Metka V
MV
Budihna
Dusan
D
Suput
D000818:Animals; D003064:Cnidarian Venoms / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D019332:Endothelin-1 / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D008387:Marine Toxins / Q000009:adverse effects* / Q000494:pharmacology; D011725:Pyridines / Q000009:adverse effects* / Q000494:pharmacology; D017466:Receptors, Endothelin; D012615:Sea Anemones / Q000737:chemistry*; D013552:Swine; D013777:Tetrazoles / Q000009:adverse effects* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000009:adverse effects* / Q000494:pharmacology
D003064:Cnidarian Venoms; D019332:Endothelin-1; D008387:Marine Toxins; D011725:Pyridines; D017466:Receptors, Endothelin; D013777:Tetrazoles; D014665:Vasodilator Agents; C012307:equinatoxin; C120582:tezosentan