Pharmacological Comparison Between the Nitrergic Responses Produced by Intramural Nerve Stimulation and Exogenous NO-Donors in Rat Gastric Fundus

Abstract

To investigate whether the nitrergic nerve-mediated smooth muscle relaxation is caused by authentic nitric oxide (NO) and is mediated via guanosine 3':5'-cyclic monophosphate (cyclic GMP), we compared the response to electrical field stimulation of nitrergic nerve (EFS) with other NO-related responses in rat gastric fundus strips. EFS, sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), and acidified NaNO₂ and inducible NO synthase (iNOS)-mediated NO all produced relaxation and elevated cyclic GMP level in rat fundus strips. However, the basal and stimulated cyclic GMP levels were significantly lower than the basal level in aorta (40±4 pmol/g wet tissue). Methylene blue and 6-anilino-5, 8-quinolinedione (LY83583), both known as soluble guanylyl cyclase inhibitors and O₂^- generators that scavenge NO, reduced the elevation of cyclic GMP level by all stimuli and inhibited 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 strips the relaxations induced by not only nitrergic nerve but also SNP and SNAP are not associated with cyclic GMP production, in contrast to the relaxations mediated by authentic NO.