FUNCTIONAL RELATION BETWEEN NITRIC-OXIDE AND NORADRENALINE FOR THE MODULATION OF VASCULAR TONE IN RAT MESENTERIC VASCULATURE

As previously reported, N-omega-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, decreased transmural field stimulatio n (TFS)-induced noradrenaline overflow from the isolated perfused rat mesenteric vasculature attached to the intestine. The decrease was att enuated by L-arginine. This suggests that NO may increase noradrenalin e release (Yamamoto et al. 1993). The present experiments with this pr eparation were done in order to monitor changes in vascular perfusion pressure caused by TFS or by noradrenaline infusion in parallel with t hose in the noradrenaline outflow caused by TFS in the presence of atr opine (0.1 mu mol/l) (to block acetylcholine-induced release of endoth elial NO) and of indomethacin (3 mu mol/l) (to inhibit L-NNA-induced p roduction of vasoconstrictor prostanoids). (1) TFS (2 - 10 Hz) caused a frequency-dependent increase in noradrenaline overflow and perfusion pressure. (2) L-NNA (10 and 30 mu mol/l) caused a concentration-depen dent inhibition of TFS-induced noradrenaline overflow, whereas the TFS -induced pressure increase was augmented by L-NNA in a concentration-d ependent manner. At any given concentration of L-NNA, the potentiation of vasoconstriction by L-NNA became greater in magnitude as the frequ ency of the TFS was raised. (3) Infusion of noradrenaline (0.38 - 6 nm ol) caused a dose-dependent increase in perfusion pressure up to a val ue comparable with that caused by TFS. The pressure increase in respon se to noradrenaline infusion was also enhanced by L-NNA, relatively, t o a greater extent than the enhancement, by L-NNA, of the pressure res ponse to TFS. (4) These effects of L-NNA were significantly attenuated by L-arginine (0.3 mmol/l) or sodium nitroprusside (1 mu mol/l). Our results suggest that NO, presumably originating from several sites, ma y stimulate the release of noradrenaline in the mesenteric vasculature and that the consequent rise in circulating noradrenaline, in turn, c auses the liberation of endothelial NO.