NO EVIDENCE FOR A SIGNIFICANT NON-NITRERGIC, HYPERPOLARIZING FACTOR CONTRIBUTION TO FIELD STIMULATION-INDUCED RELAXATION OF THE MOUSE ANOCOCCYGEUS

1 The aim of the study was to determine whether a nerve-derived hyperp olarizing factor (NDHF) might contribute to non-adrenergic, non-cholin ergic (NANC) relaxations of the mouse anococcygeus when low concentrat ions of contractile agent are used to raise tone and low frequencies o f field stimulation applied: such a non-nitrergic NDHF has been propos ed to contribute to NANC relaxations of the rat anococcygeus and guine a-pig taenia coli. 2 Phenylephrine (0.1-100 CIM) Produced concentratio n-related contractions of the mouse isolated anococcygeus muscle; 0.2 mu M phenylephrine (EC26) was used to raise tone in subsequent experim ents. 3 Field stimulation (0.5, 1.0 and 5.0 Hz) produced frequency-dep endent relaxations of phenylephrine-induced tone. In the presence of t he nitric oxide synthase inhibitor L-N-G-nitro-arginine (L-NOARG; 100 mu M), the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxodiazolo[4, 3-a]quinoxalin-1-one (ODQ; 5 mu M), or a combination of these two drug s, relaxations to field stimulation were abolished at all frequencies studied. Relaxations to sodium nitroprusside (0.01-5 mu M) were unaffe cted by L-NOARG but strongly inhibited by ODQ; neither enzyme inhibito r affected relaxations to 8-Br-cyclic GMP (10 mu M). 4 Nifedipine (1 m u M) reduced the contractile response to 0.2 mu M phenylephrine by 38% ; however, it had no effect on NANC relaxations. 5 It is concluded tha t NANC relaxations of the mouse anococcygeus are purely nitrergic and that there is no significant contribution from a putative NDHF.