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

Abstract

Airway function is largely preserved during exercise or isocapnic hyperventilation in humans and guinea pigs despite likely changes in airway milieu during hyperpnea. It is only on cessation of a hyperpneic challenge that airway function deteriorates significantly. We tested the hypothesis that nitric oxide, a known bronchodilator that is produced in the lungs and bronchi, might be responsible for the relative bronchodilation observed during hyperventilation (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 ventilation groups included normal ventilation [40 breaths/min, 6 ml/kg tidal volume (VT)], 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 oxide was slightly but significantly increased by HV in the saline groups. However, inhibition of nitric oxide production had no significant effect on rate of rise of respiratory system resistance (Rrs) during HV or on the larger rise in Rrs seen 6 min after HV. We conclude that nitric oxide synthase inhibition has no effect on changes in Rrs, either during or after HV in guinea pigs.

Role of airway endogenous nitric oxide on lung function during and after exercise in mild asthma

“…Thus, during exercise, there was a small parallel shift up in the RL values on the L-NMMA treatment compared with the saline treatment day, but the rate of rise in RL was the same. The significant slow rise in RL during hyperpnea is consistent with our laboratory's earlier studies in both humans (8,34) and guinea pigs (33,35), which showed that airway function deteriorates slowly during hyperpnea of constantload exercise or isocapnic hyperventilation. That inhaled L-NMMA did not prevent the drop in RL early in exercise indicates that the fall in RL was not caused by an increase in endogenous NO production in airways at the onset of hyperpnea.…”

“…However, there is some debate about its role both in normal airways and in asthmatic subjects. Numerous studies demonstrated no change in baseline lung function after NO synthase inhibition in either animals (22,33,39) or Fig. 3.…”

“…Our laboratory has shown in other studies that prostaglandins do not have a major influence on airway smooth muscle during exercise in humans (7) or during hyperventilation in guinea pigs (35). Similarly, NO synthase inhibition has little effect on the changes in airway function during hyperventilation in the guinea pig (33). The bronchodilator role of NO in humans during the hyperpnea of exercise has not been explored.…”