Abstract
Electrical field stimulation (EFS) induced a relaxation response in female rabbit urethral smooth muscle strips precontracted with phenylephrine. The relaxation response was inhibited by tetrodotoxin, but not by atropine, propranolol, or hexamethonium. Thus, the relaxation response results from stimulation of inhibitory non-adrenergic, non-cholinergic nerves. The EFS induced relaxation response was inhibited by an inhibitor of nitric oxide biosynthesis, NG-nitro-L-arginine. This inhibition was overcome by addition of a precursor of nitric oxide, L-arginine. An inhibitor of soluble guanylate cyclase, methylene blue, but not an inhibitor of soluble adenylate cyclase, SQ22536 reduced the relaxation response. And a selective cyclic GMP phosphodiesterase inhibitor, M & B22948 and also a non selective phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine, potentiated the relaxation response. Cyclic GMP, but not cyclic AMP contents were significantly elevated by EFS in urethral smooth muscle strips. These data demonstrate that agents which affect the biosynthesis of nitric oxide are associated with the urethral relaxation evoked by EFS, and that cyclic GMP but not cyclic AMP mediates the relaxation response.
