Impaired bronchomotor responses to field stimulation in guinea-pigs with cisplatin-induced neuropathy

Pre-treatment with cisplatin (3 mg/kg) i.p, once a day over 6 days induced sensory neuropathy as confirmed by femoral nerve conduction velocity test a nd significantly decreased contractions induced by electrical field stimula tion (100 stimuli, 20 V, 0.1 ms, 20 Hz) in isolated main bronchial rings fr om guinea-pigs. The field stimulation-induced non-adrenergic, non-cholinerg ic (NANC) relaxations, however, were amplified in rings from animals with c isplatin neuropathy. The NANC relaxation response was completely blocked by 30 mu M N-G-nitro-L-arginine methyl ester in preparations from both contro l and cisplatin-treated animals. Superoxide dismutase (40 units/ml) was wit hout effect on NANC relaxation in control rings, however, it substantially decreased NANC relaxation in preparations from animals with cisplatin neuro pathy. These results show that cisplatin-induced sensory neuropathy is acco mpanied by attenuation of neural bronchoconstriction and an enhanced NANC r elaxation. The latter is in part attained by an increased peripheral supero xide production. (C) 2000 Elsevier Science B.V. All rights reserved.