Evidence for a differential release of nitric oxide and vasoactive intestinal polypeptide by nonadrenergic noncholinergic nerves in the rat gastric fundus.

The roles of vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) in nonadrenergic noncholinergic (NANC) nerve-mediated relaxations were investigated in longitudinal muscle strips of the rat gastric fundus. Transmural stimulation (1-16 Hz for 2 min), VIP and noradrenaline evoked a prolonged relaxation of the rat gastric fundus, whereas NO evoked a transient relaxation. Only the electrically induced responses were blocked by tetrodotoxin. The inhibitor of NO biosynthesis NG-nitro-L-arginine (L-NNA) preferentially inhibited the relaxations induced by low frequency stimulation. In contrast, trypsin mainly reduced the electrically induced relaxations to high frequency stimulation; the NANC relaxations resistant to trypsin were further inhibited by L-NNA. VIP-induced relaxations were abolished by trypsin, but remained unaffected by L-NNA. NO- or noradrenaline-induced relaxations were not inhibited by either L-NNA or trypsin alone, whereas the combination of L-NNA and trypsin slightly reduced the noradrenaline-induced responses. These results suggest that NANC responses in the rat gastric fundus at low frequency are mediated mainly by NO, whereas at higher frequency NO together with a peptide, probably VIP, are released.