We examined the characteristics of the non-adrenergic non-cholinergic (NANC) nerve induced relaxation and the possible interaction between nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) on the basal tone of the circular muscle of the rat gastric fundus. Electrically induced NANC relaxations were partly inhibited by N-omega-nitro-L-arginine (100 muM), whereas sodium nitroprusside (SNP; 10 muM) and VIP (5 nM) induced relaxations were not affected. 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT; 5 muM) also inhibited the responses to electrical stimuli to a similar extent as N-omega-nitro-L-arginine but not VIP. However, AMT plus N-omega-nitro-L-arginine did not give an additional inhibition above that of each drug alone on NANC relaxations, and dexamethasone (10 muM) had no effect on NANC nerve induced relaxations. 1H-[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 muM), a selective inhibitor of guanylate cyclase, abolished the responses to NANC nerve stimulation and SNP, while VIP responses were not influenced. N-ethylmaleimide (100 muM), an adenylate cyclase inhibitor, attenuated relaxations to NANC nerve stimulation, VIP and isoproterenol (I nM), while having no effect on those to SNP, but in combination with N-omega-nitro-L-arginine, there was no additional inhibition on the responses to nerve stimulation. Alpha-chymotrypsin (10 u ml(-1)) severely diminished VIP induced relaxations, but did not reduce electrical responses. In conclusion, these results suggest that NO is involved in the relaxations induced by short-term electrical stimulation. However, another possible unidentified transmitter that can trigger the accumulation of cyclic GMP is not entirely ruled out and there is no interaction between NO and VIP in the circular muscle strip of the rat gastric fundus, even in the basal state of the tissue. (C) 2001 Academic Press.