Effect of nitric oxide synthesis inhibition with nebulized L-NAME on ventilation-perfusion distributions in bronchial asthma

• Published in: The European respiratory journal Vol. 12; no. 4; pp. 865 - 871
• Main Authors: Gomez, FP, Barbera, JA, Roca, J, Iglesia, R, Ribas, J, Barnes, PJ, Rodriguez-Roisin, R
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01.10.1998; Maney
• Subjects: Administration, Inhalation; Adult; Airway Resistance - drug effects; Asthma - drug therapy; Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; Cross-Over Studies; Enzyme Inhibitors - administration & dosage; Female; Humans; Male; Medical sciences; NG-Nitroarginine Methyl Ester - administration & dosage; Nitric Oxide - analysis; Nitric Oxide - metabolism; Pneumology; Pulmonary Gas Exchange - drug effects; Reference Values; Ventilation-Perfusion Ratio - drug effects; Human; Regional perfusion; Respiratory disease; Enzyme; Lung; Enzyme inhibitor; Exploration; Asthma; Pulmonary vessel; Ligases; Aerosols; Ventilation; Circulatory system; Obstructive pulmonary disease; Hemodynamics; Gas exchange; Nitrogen Oxides
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.98.12040865

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 production may be detrimental for optimal V'A/Q' balance owing to the potential inhibition of hypoxic pulmonary vasoconstriction. This study was undertaken to investigate the relationship between the concentration of NO in exhaled air and the degree of gas-exchange impairment and to assess the effect of nebulized N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthesis, on gas exchange in patients with asthma. Twelve patients (four females and eight males, aged 31+/-5 yrs) with clinically stable asthma (forced expiratory volume in one second (FEV1) 80+/-5%) not treated with glucocorticoids and increased 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 placebo or L-NAME (10(-1) M) nebulization; in eight patients pulmonary haemodynamics were also measured. At baseline no relationships between exhaled NO and gas-exchange measurements were shown. Nebulized L-NAME induced a significant decrease in exhaled NO (p< 0.001), which was maximal at 90 min (-55+/-5%). However, after L-NAME no changes in Rrs, arterial oxygen tension, the alveolar-arterial pressure difference in oxygen or V'A/Q' distributions were shown and nebulized L-NAME did not modify pulmonary artery pressure. In conclusion, the degree of gas-exchange impairment in stable asthma is not related to nitric oxide concentration in exhaled air and nitric oxide synthesis inhibition with N(G)-nitro-L-arginine methyl ester does not alter gas exchange or pulmonary haemodynamics, such that ventilation-perfusion disturbances do not appear to be related to an increased synthesis of nitric oxide in the airways.