NEUROGENIC VASODILATION IN RABBIT HINDLIMB MEDIATED BY TACHYKININS AND NITRIC-OXIDE

We investigated the role of nitric oxide (NO) in the mediation of nerv e stimulation-induced vasodilation in skeletal muscle. Hindlimb blood flow and vascular resistance were measured in pentobarbital-anesthetiz ed, paralyzed, and guanethidine-treated rabbits. Centrifugal electrica l stimulation of the sciatic nerve bundle induced reproducible, freque ncy-, voltage-, and pulse duration-dependent decrements in vascular re sistance. The tachykinin antagonist CP-96,345 (I mg/kg intravenously, i.v.) attenuated the vasodilation induced by intraarterially (i.a.) ad ministered substance P but not by adenosine. Furthermore, CP-96,345 at tenuated the decrease in vascular resistance in response to nerve stim ulation, from 22.9 +/- 3.2 to 4.5 +/- 4.1% of control resting resistan ce (p < 0.005), without affecting basal vascular resistance. An inhibi tor of NO formation, N(omega)-nitro-L-arginine methyl ester (L-NAME, 3 0 mg/kg i.v.), increased vascular resistance from 6.1 +/- 0.5 to 9.1 /- 1.2 resistance units (p < 0.05) and significantly attenuated the va scular response to i.a. administered substance P but not adenosine. Fi nally, nerve stimulation-induced reduction in vascular resistance was attenuated by L-NAME, from 22.6 +/- 2.7 to 7.0 +/- 1.0% of control (p < 0.001). These findings suggest that tachykinins and NO are involved in mediation of vasodilation in response to the present type of nerve stimulation. The data are consistent with the hypothesis that NO is pr oduced subsequent to neural release of tachykinin-type transmitter(s).