VASCULAR ACETYLCHOLINE RESPONSE DURING CHRONIC NO SYNTHASE INHIBITION- IN-VIVO VERSUS IN-VITRO

Objective: The aim of this study was to compare the response to NO-med iated vasodilators in vivo and in vitro during chronic NO synthase inh ibition. Methods: N-G-Nitro-L-arginine-methyl ester (L-NAME, 0.4 g/l) or vehicle was administered in the drinking water for 6 weeks to male Wistar rats weighing 220-240 g. The effect of acetylcholine and sodium nitroprusside was examined in vivo, on systemic blood pressure and he art rate and in vitro, on the precontracted isolated mesenteric artery . The in vivo response to both vasodilators was examined in awake rats monitored by an indwelling catheter in the femoral artery. Isolated s egments of the third-generation mesenteric artery were examined in vit ro with a Mulvany dual myograph after precontraction with noradrenalin e. Results: In isolated mesenteric arteries obtained from rats chronic ally treated with L-NAME, the initial relaxant response to acetylcholi ne was significantly decreased whereas that to sodium nitroprusside wa s enhanced. A late acetylcholine-induced contractile response was pres ent and abolished by indomethacin. In vive, the hypotensive action of sodium nitroprusside was also enhanced in the L-NAME-treated rats. Ace tylcholine reduced blood pressure in the L-NAME-treated hypertensive a nimals more than in normotensive controls, but less than in control ra ts infused intravenously with noradrenaline at a dose increasing their blood pressure to hypertensive levels. Conclusions: The NO-mediated v asodilation induced by acetylcholine is attenuated during chronic NO s ynthase inhibition, both in vive and in vitro. The blunted hypotensive response to acetylcholine can be demonstrated only if blood pressure of control rats is acutely increased to hypertensive levels.