REGULATION OF BRADYKININ SENSITIVITY IN PERIPHERAL SENSORY FIBERS OF THE NEONATAL RAT BY NITRIC-OXIDE AND CYCLIC-GMP

Bradykinin-induced activation of peripheral sensory fibres was studied using an in vitro preparation of the neonatal rat spinal cord with at tached tail. Noxious heat stimulation, as well as the applications of bradykinin and capsaicin, to the tail evoked reproducible responses re corded as a depolarization of a lumbar ventral root. Prolonged adminis tration of a supramaximal concentration of bradykinin invariably induc ed a complete but selective desensitization to a subsequent bradykinin challenge. Bradykinin-induced desensitization was significantly atten uated by concanavalin-A and the effect of concanavalin-A was prevented by alpha-methyl mannoside. Both cyclic GMP and sodium nitroprusside i nduced a long lasting reduction of bradykinin responsiveness in periph eral fibres. The effect of nitroprusside was prevented by concanavalin -A, and by methylene blue, an inhibitor of guanylyl cyclase. Methylene blue also reduced bradykinin-induced desensitization. L-arginine, but not D-arginine, induced a desensitization to bradykinin. On the other hand, 7-nitroindazole (7-NI, 200-500 nM), an inhibitor of NOS, reduce d the desensitization of bradykinin responses but higher concentration s of 7-NI (IC50 = 6.7 +/- 0.9 mu M) selectively attenuated responses t o bradykinin. The effects of 7-NI were attenuated by L-arginine pretre atment. These data suggest that bradykinin-induced desensitization of peripheral sensory fibres is mediated in part via NO and cyclic GMP de pendent mechanisms; possibly NO production is required for guanylate c yclase activation.