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 stimulation (TFS)-induced noradrenaline overflow from the isolated perfused rat mesenteric vasculature attached to the intestine. The decrease was attenuated by L-arginine. This suggests that NO may increase noradrenaline release (Yamamoto et al. 1993). The present experiments with this preparation were done in order to monitor changes in vascular perfusion pressure caused by TFS or by noradrenaline infusion in parallel with those in the noradrenaline outflow caused by TFS in the presence of atropine (0.1 mu mol/l) (to block acetylcholine-induced release of endothelial NO) and of indomethacin (3 mu mol/l) (to inhibit L-NNA-induced production 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-dependent inhibition of TFS-induced noradrenaline overflow, whereas the TFS-induced pressure increase was augmented by L-NNA in a concentration-dependent manner. At any given concentration of L-NNA, the potentiation of vasoconstriction by L-NNA became greater in magnitude as the frequency of the TFS was raised. (3) Infusion of noradrenaline (0.38 - 6 nmol) caused a dose-dependent increase in perfusion pressure up to a value comparable with that caused by TFS. The pressure increase in response to noradrenaline infusion was also enhanced by L-NNA, relatively, to a greater extent than the enhancement, by L-NNA, of the pressure response 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, may stimulate the release of noradrenaline in the mesenteric vasculature and that the consequent rise in circulating noradrenaline, in turn, causes the liberation of endothelial NO.