Effect of nitric oxide synthase inhibitor on allergen- and hyperventilation-induced bronchoconstriction in guinea-pigs

To elucidate the role of endogenous nitric oxide (NO) in allergen- (AIB) an d hyperventilation-induced bronchoconstriction (NIB), the effects of an NO synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), on AIB and HIB were studied in guinea-pigs, In the AIB group, 21 anaesthetized guinea-pigs, actively sensitized with 1% ovalbumin, were challenged with aerosolized 0.1% ovalbumin solution under mechanical ventilation. In the HIB group, 14 guinea-pigs were challenged wi th hyperventilation (tidal volume of 12 mL.kg(-1) at 150 breaths.min(-1) wi th 21% O-2 and 5% CO2 dry gas) for 5 min. In both groups,lang resistance (R b.) was measured using a pressure-volume-sensitive body plethysmograph, wit h or without L-NAME pretreatment (8 mg.kg(-1) i.v, followed by 2 mg.kg(-1) min(-1) i.v). The NO precursor, L-arginine was injected at a rate of 15 mg. kg(-1) min(-1) after L-NAME injection (10 mg.kg(-1)) in the AIB group. The results were as follows, In the AIB group, the maximal Rr. change was s ignificantly, potentiated by pretreatment with L-NAME, This potentiating ef fect of L-NAME was reversed by L-arginine. In the HIB group, the pretreatme nt with L-NAME had net effect on increases in RL. These findings suggest th:lt endogenous nitric oxide may play an important role in the modulation of:allergen-, but not hyperventilation-induced bronc hoconstriftion in guinea-pigs.