Role of nitric oxide in hyperpnea-induced bronchoconstriction and airway microvascular permeability in guinea pigs

Abstract

ABSTRACTThe present study aimed to evaluate the role of nitric oxide (NO) on hyperpnea-induced bronchoconstriction (HIB) and airway microvascular hyperpermeability (AMP). Sixty-four guinea pigs were anesthetized, tracheotomized, cannulated, and connected to animal ventilator to obtain pulmonary baseline respiratory system resistance (Rrs). Animals were then submitted to 5 minutes hyperpnea and Rrs was evaluated during 15 minutes after hyperpnea. AMP was evaluated by Evans blue dye (25 mg/kg) extravasation in airway tissues. Constitutive and inductible NO was evaluated by pretreating animals with NG-nitro-l-arginine methyl ester (l-NAME) (50 mg/kg), aminoguadinine (AG) (50 mg/kg), and l-arginine (100 mg/kg) and exhaled NO (NOex) was evaluated before and after drug administration and hyperpnea. The results show that l-NAME potentiated (57%%) HIB and this effect was totally reversed by l-arginine pretreatment, whereas AG did not have effect on HIB. l-NAME decreased basal AMP (48%%), but neither l-NAME nor AG had any effect on hyperpnea-induced AMP. NOex levels were decreased by 50%% with l-NAME, effect that was reversed by l-arginine treatment. These results suggest that constitutive but not inducible NO could have a bronchoprotective effect on HIB in guinea pigs. The authors also observed that neither constitutive nor inducible NO seems to have any effect on hyperpnea-induced AMP.