Protection from diaphragmatic fatigue by nitric oxide synthase inhibitor in dogs

Abstract

The role of endogenous nitric oxide (NO) in producing diaphragmatic fatigue was examined in 26 anaesthetized, mechanically ventilated dogs divided into four groups. In Group Ia (n = 5), dogs without fatigue received only Ringer's lactate solution. In group Ib (n = 5), dogs without fatigue were given IV L-arginine analog N(ω)-nitro-L-arginine methyl ester (L-NAME) 10 mg kg-1 to inhibit NO synthase (NOS). Groups IIa and IIb (n = 8 of each) received the same doses of IV lactate and L-NAME as Groups Ia and Ib effectively. Following administration of the IV solution, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed in each group by measuring transdiaphragmatic pressure (Pdi). No difference in Pdi was observed between Groups Ia and Ib. After the fatigue-producing period, in Group IIa, Pdi at a low frequency (100 Hz) stimulation did not change. In Group IIb, given L-NAME before producing fatigue, Pdi at both stimuli did not change. In conclusion, L-NAME inhibits the production of diaphragmatic fatigue. This finding suggests that endogenous NO plays an important role in producing diaphragmatic fatigue.