INVOLVEMENT OF ENDOTHELIUM-DERIVED NO IN THE BASAL TONE AND IN THE VASODILATOR RESPONSES TO MUSCARINIC AGONISTS IN THE RAT ISOLATED MESENTERIC ARTERIAL BED

To investigate the involvement of nitric oxyde (NO) derived from endot helial cells in the control of vascular tone in the rat mesenteric vas cular bed, the effects of different procedures known to interfere with the NO-cyclic GMP pathway were evaluated both on the basal tone and o n the vasodilatory responses to four muscarinic agonists. To this aim, rat isolated mesenteric vascular beds were perfused at constant press ure. Water infusion significantly increased the resting perfusion pres sure whereas L-NOARG, L-NAME and methylene blue were devoid of effect. In noradrenaline-preconstricted vascular bed, the perfusion pressure was significantly increased after water or L-NAME infusion. The vasodi lator response induced by subsequent addition of acetylcholine in bolu s was not significantly modified by pre-treatment with indomethacin bu t was significantly reduced by water infusion. Reponses to acetylcholi ne and to three other muscarinic agonists -carbachol, oxotremorine or McNeil A 343- were assessed. Incubation with L-NAME did not modify the initial peak falls of the agonists except for McNeil A 343, whereas i t significantly reduced the area under the pressure trace for all the substances. The latter effect was reversed after a subsequent incubati on with L-Arginine. Finally, L-NAME strongly and significantly increas ed the drop in perfusion pressure and the area under the pressure trac e following bolus of glyceryl trinitrate. These results suggest that i n the mesenteric arterial bed of the rat, which can be considered as a resistant arteries preparation, basal tone appears to be controlled b y a factor other than NO. Moreover, the vasodilator responses of musca rinic agonists are affected by L-NAME in their second late sustained p hase only, which probably relies on a de novo synthesis of endothelium derived-NO. Finally, endothelium derived-NO exerts inhibitory effects both on the sensitivy of the vascular smooth muscle to glyceryl trini trate and on the magnitude of its contraction in the presence of norad renaline, two types of effects which are sensitive to L-NAME.