Title Nitric oxide modulates biphasic contractile response of guinea pig vas deferens to electrical field stimulation

Electrical field stimulation (EFS) produced a biphasic contractile response; viz. initial rapid phasic contraction and second slow tonic contraction, in isolated guinea pig vas deferens. Pretreatment with the substrate of nitric oxide (NO) synthase (NOS), 1 mM L-arginine (L-ARG), augmented both the initial rapid and the second slow contractile responses to EFS (5 Hz, 0.5 msec, 30 V, for 30 sec) . The increase of stimulation frequency from 5 Hz to 10 Hz or 20 Hz tended to attenuate the augmented responses. On the contrary, pretreatment with an inhibitor of NOS, 0.1 mM NG-nitro-L-arginine (L-NNA) suppressed both the initial rapid and the second slow contractile responses to EFS. The suppressive effect on the initial rapid contraction was also attenuated by the increase of stimulation frequency from 5 Hz or 10 Hz to 20 Hz. Contractile response to exogenously administered 1 mM adenosine triphosphate (A TP) tended to be slightly increased and decreased by the treatment with 1 mM L-ARG and 0.1 mM L-NNA, respectively. Contractile response to exogenously administered 10 pM noradrenaline (NA) was almost unaffected by the treatment with 1 mM L-ARG, while the treatment with 0.1 mM L-NNA slightly depressed the response. Potentiated contractile response to 1 mM ATP in the presence of 10 pM NA was further potentiated by the treatment with 1 mM L-ARG, while the response was almost unaffected by the treatment with 0.1 mM L-NNA. These findings may indicate that NO acts mainly on presynaptic site and increases the release of chemical transmitter, ATP or prevents the inactivation of ATP. Also, NO may act, at least in part, on postsynaptic site and potentiates the contractile response to A TP in the presence of N A. tpGG5MlU, t7}1liij JjJ, tp:l:amUi§ Correspondence to: Hironori Nakanishi, Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan. E-mail: pharm@fmu.ac.jp