Thaliporphine protects ischemic and ischemic-reperfused rat hearts via an NO-dependent mechanism

In ischemia or ischemia-reperfusion (I/R), nitric oxide (NO) can potentiall y exert several beneficial effects. Thaliporphine, a natural alkaloid with Ca2+ channel-activating and Na+/K+ channel-blocking activities, increased N O levels and exerted cardioprotective action in ischemic or I/R rats. The r ole of NO in the cardioprotective actions of thaliporphine was assessed. Th e severity of rhythm disturbances and mortality in anesthetized rats with e ither coronary artery occlusion for 30 min, or 5 min followed by 30-min rep erfusion, were monitored and compared in thaliporphine- vs. placebo-treated groups. Thaliporphine treatment significantly increased NO and decreased l actate dehydrogenase (LDH) levels in the blood during the end period of isc hemia or I/R. These changes in NO and LDH levels by thaliporphine were asso ciated with a reduction in the incidence and duration of ventricular tachyc ardia (VT) and ventricular fibrillation (VF) during ischemic or I/R period. The mortality of animals was also completely prevented by 1 x 10(-8) moles /kg of thaliporphine. In animals subjected to 4 h of left coronary artery o cclusion, 1 x 10(-7) moles/kg of thaliporphine dramatic reduced cardiac inf arct zone from 46 +/- 6% to 7.1 +/- 1.9%. Inhibition of NO synthesis with 3 .7 x 10(-6) moles/kg of N-omega-nitro-L-arginine methyl ester (L-NAME) abol ished the beneficial effects of thaliporphine during 30 min or 4 h myocardi al ischemia. However, the antiarrhythmic activity and mortality reduction e fficacy of thaliporphine during reperfusion after 5 min of ischemia was onl y partially antagonized by L-NAME. These results showed that thaliporphine efficiently exerted the cardioprotections either in acute or prolonged coro nary artery occlusion or occlusion-reperfusion situations. The fact that th aliporphine induced cardioprotective effects were abrogated by L-NAME indic ates that NO is an important mediator for the cardioprotective effects of t haliporphine in acute or prolonged ischemia, whereas antioxidant activities may contribute to the protection of I/R injury. (C) 2001 Wiley-Liss, Inc.