Pharmacological comparison between the nitrergic responses produced by intramural nerve stimulation and exogenous NO-donors in rat gastric fundus

To investigate whether the nitrergic nerve-mediated smooth muscle relaxatio n is caused by authentic nitric oxide (NO) and is mediated via guanosine 3' :5'-cyclic monophosphate (cyclic GMP), we compared the response to electric al field stimulation of nitrergic nerve (EFS) with other NO-related respons es in rat gastric fundus strips. EFS, sodium nitroprusside (SNP), S-nitroso -N-acetylpenicillamine (SNAP), and acidified NaNO2 and inducible NO synthas e (iNOS)-mediated NO all produced relaxation and elevated cyclic GMP level in rat fundus strips. However, the basal and stimulated cyclic GMP levels w ere significantly lower than the basal level in aorta (40+/-4 pmol/g wet ti ssue). Methylene blue and 6-anilino-5,8-quinolinedione (LY83583), both know n as soluble guanylyl cyclase inhibitors and O-2(-) generators that scaveng e NO, reduced the elevation of cyclic GMP level by all stimuli and inhibite d the relaxations only in response to NaNO2 and iNOS-mediated NO but not to the other stimuli. These results suggest that in the rat gastric fundus st rips the relaxations induced by not only nitrergic nerve but also SNP and S NAP are not associated with cyclic GMP production, in contrast to the relax ations mediated by authentic NO.