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 and significantly decreased contractions induced by electrical field stimulation (100 stimuli, 20 V, 0.1 ms, 20 Hz) in isolated main bronchial rings from guinea-pigs. The field stimulation-induced non-adrenergic, non-cholinergic (NANC) relaxations, however, were amplified in rings from animals with cisplatin neuropathy. The NANC relaxation response was completely blocked by 30 microM N(G)-nitro-L-arginine methyl ester in preparations from both control and cisplatin-treated animals. Superoxide dismutase (40 units/ml) was without effect on NANC relaxation in control rings, however, it substantially decreased NANC relaxation in preparations from animals with cisplatin neuropathy. These results show that cisplatin-induced sensory neuropathy is accompanied by attenuation of neural bronchoconstriction and an enhanced NANC relaxation. The latter is in part attained by an increased peripheral superoxide production.