Cobra cardiotoxin induced initial transient relaxation followed by contraction in rat aortic rings

Abstract

The mechanism of actions of cardiotoxin (CTX), a basic polypeptide purified chronutographically from cobra venom, on vascular contraction was investigated. CTX (10 μM)-induced small, variable and transient relaxation in endothelnim-intact aortic rings followed by large, consistent and sustained contraction. Rings precontracted with 1 μM phenylephrme (PE) showed substantial transient relaxation when CTX was added to the plateau phase of the PE-contraction. Pre-incubation of rings with L-NAME (NO synthase inhibitor) inhibited the relaxation indicating NO is responsible for the relaxation. CTX also caused contraction in Ca 2+-dependent manner with maximal contractile force at 0.5 mM but high CV 2+ (7 mM) totally inhibited the CTX-induced contraction. The CTX inducedcontraction in endothelhun-intact and -denuded aortic rings showed no difference in maximal tension development indicating the loss of functional endothelial cells following CTX treatment. ACh-induced relaxation was lost after CTX treatment but was retained partially when high Ca 2+ was present prior to the addition of CTX. Not only high Ca 2+ could inhibit the CTX-induced contraction so did Ni 2+, Tetrandrine, SK&F 96365 and Nifedipine. Hence, we conclude that CTX triggers the release of MO from the damaged endothelitun and the subsequent contractile response is probably due to enhanced membrane leak to Co 2+ in damaged smooth muscle cells. High Co 2+ and other Co 2+ antagonists protect endothelial and smooth muscle cells from CTX-induced damage via its action on Co 2+-channels and Co 2+-binding site. (Supported by HKRGC).