Role of nitric oxide during hyperventilation-induced bronchoconstriction in the guinea pig

Airway function is largely preserved during exercise or isocapnic hypervent ilation in humans and guinea pigs despite likely changes in airway milieu d uring hyperpnea. It is only on cessation of a hyperpneic challenge that air way function deteriorates significantly. We tested the hypothesis that nitr ic oxide, a known bronchodilator that is produced in the lungs and bronchi, might be responsible for the relative bronchodilation observed during hype rventilation (HV) in guinea pigs. Three groups of anesthetized guinea pigs were given saline and three groups given 50 mg/kg N-G-monomethyl-L-arginine (L-NMMA), a potent nitric oxide synthase inhibitor. Three isocapnic ventil ation groups included normal ventilation [40 breaths/min, 6 ml/kg tidal vol ume (V-T)], increased respiratory rate only (150 breaths/min, 6 ml/kg VT), and increased respiratory rate and increased volume (100 breaths/min, 8 ml/ kg VT). L-NMMA reduced expired nitric oxide in all groups. Expired nitric o xide was slightly but significantly increased by HV in the saline groups. H ow ever, inhibition of nitric oxide production had no significant effect on rate of rise of respiratory system resistance (Rrs) during HV or on the la rger rise in Rrs seen 6 min after HV. We conclude that nitric oxide synthas e inhibition has no effect on changes in Rrs, either during or after HV in guinea pigs.