Nitric oxide, an enteric nonadrenergic‐noncholinergic relaxant transmitter: evidence using phosphodiesterase V and nitric oxide synthase inhibition

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Abstract
The effects of NG‐nitro‐L‐arginine (L‐NOARG), a nitric oxide synthase inhibitor, and SK&F 96231, a phosphodiesterase type V inhibitor, on electrical field stimulated (EFS) nonadrenergic noncholinergic (NANC) relaxations of rat fundal strips, guinea‐pig isolated ileum longitudinal muscle with intact myenteric plexus, and guinea‐pig taenia caeci were investigated Reproducible repeated control random EFS frequency‐response curves were obtained for all three tissues > Depending on the frequency of stimulation, L‐NOARG (10−4‐5 × 10−3M) caused either a complete or partial inhibition of the NANC‐induced relaxations of the rat fundal strips and the guinea‐pig isolated ileum longitudinal muscle with intact myenteric plexus, but not of the guinea‐pig taenia caeci. The inhibitory action of L‐NOARG was partially or totally reversed, depending on the tissue, by L‐arginine (5 × 10−3 M) SK&F 96231 (10−6‐10−4M) caused a concentration‐ and frequency‐dependent potentiation of both the size and duration of the EFS‐induced NANC relaxant response of rat fundal strips and guinea‐pig isolated ileum longitudinal muscle with intact myenteric plexus, but not of the guinea‐pig taenia caeci Zaprinast, another phosphodiesterase type V inhibitor (10−6‐10−4 M) caused a concentration‐ and frequency‐dependent potentiation of the NANC relaxant responses to EFS of rat fundal strips SK&F 96231 and zaprinast alone (10−6‐10−4M) caused a concentration‐dependent relaxation of the agonist‐induced tone of all three tissues with the maximum degree of relaxation found to be in the order stomach < ileum < caecum. This is the reverse order for ability of SK&F 96231 to potentiate relaxant responses to EFS These results suggest NO is involved in the NANC nerve‐mediated relaxation of rat fundal strips and guinea‐pig isolated ileum longitudinal muscle with intact myenteric plexus, but not the guinea‐pig taenia caeci.

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