Effects of acute caffeine administration on NOS and Bax/Bcl2 expression in the myocardium of rat.

Caffeine is the most frequently ingested neuroactive drug in the world and it is largely used to delay fatigue and improve physical activity. Caffeine can modulate NO synthesis in cells and may influence muscular function by modifying the cellular cycle life-death. There is little data concerning the relationship between Caffeine in the heart, NOS expression and apoptosis and no data regarding the acute effect of high doses of Caffeine in the in vivo myocardium. We therefore studied hemodynamic NOS and Bax/Bcl2 expression in the rat myocardium after a single Cafffeine administration. Thirty-two male rats were divided into 6 groups: the first was iv-injected with Caffeine (16mg/kg), the 2nd with Caffeine+LNAME (30 mg/kg), the 3rd with Caffeine+Larg (0.5 g/kg), the 4th with Caffeine+LNAME+LArg and finally the 5th with saline. Mean arterial blood pressure (MAP) was monitored for 30’, then the animals were killed. The 6th group was injected with Caffeine and killed after 2h. The hearts were isolated and processed by immunohistochemistry. We found that Caffeine increased MAP temporarily while Caffeine+LNAME increased it for a longer period. In the control myocardium, all NOS isoforms were expressed. The Bcl2 were strongly expressed inside the perinuclear cytoplasm whereas Bax was very faintly detectable in the peripheral cytoplasm. In Caffeine and Caffeine+LNAME treated animals, NOS expression disappeared. Bax and Bcl2 expression did not vary. The Larg administration reversed these Caffeine and L-NAME effects on NOS expression. Two hours after Caffeine, NOS expression increased and Bax and Bcl2 expression did not vary, although Bcl2 was mainly expressed in the peripheral cytoplasm. We conclude that improved Caffeine-induced physical performance could also be related to Caffeine’s ability to interfere with endogenous myocardial NO synthesis. Furthermore, we suggest that myocardial cells plays an effective anti-apoptotic role against acute Caffeine administration.