EFFECT OF NITRIC-OXIDE SYNTHESIS INHIBITION WITH NEBULIZED L-NAME ON VENTILATION-PERFUSION DISTRIBUTIONS IN BRONCHIAL-ASTHMA

Patients with clinically stable asthma may show ventilation-perfusion (V'A/Q') mismatch, Nitric oxide (NO), a potent endogenous vasodilator, is increased in exhaled air of asthmatics, Such an increased NO produ ction may be detrimental for optimal V'A/Q' balance owing to the poten tial inhibition of hypoxic pulmonary vasoconstriction, This study was undertaken to investigate the relationship between the concentration o f NO in exhaled air and the degree of gas-exchange impairment and to a ssess the effect of nebulized Nc-nitro-L-arginine methyl ester (L-NAME ), a competitive inhibitor of NO synthesis, on gas exchange in patient s with asthma, Twelve patients (four females and eight males, aged 31/-5 yrs) with clinically stable asthma (forced expiratory volume in on e second (FEV1) 80+/-5%) not treated with glucocorticoids and increase d exhaled NO (58+/-9 parts per billion (ppb)) were studied. Exhaled NO , respiratory system resistance (Rrs), arterial blood gases and V'A/Q' distributions were measured before and 30, 60, 90 and 120 min after p lacebo or L-NAME (10(-1) M) nebulization; in eight patients pulmonary haemodynamics were also measured, At baseline no relationships between exhaled MO and gas-exchange measurements were shown. Nebulized L-NAME induced a significant decrease in exhaled NO (p<0.001), which was max imal;at 90 min (-55+/-5%). However, after L-NAME no changes in Rrs, ar terial oxygen tension, the alveolar-arterial pressure difference in ox ygen or V'A/Q' distributions were shown and nebulized L-NAME did not m odify pulmonary artery pressure. In conclusion, the degree of gas-exch ange impairment in stable asthma is not related to nitric oxide concen tration in exhaled air and nitric oxide synthesis inhibition with N-G -nitro-L-arginine methyl ester does not alter gas exchange or pulmonar y haemodynamics, such that ventilation-perfusion disturbances do not a ppear to be related to an increased synthesis of nitric oxide in the a irways.