Endogenous NO does not regulate baseline pulmonary pressure, but reduces acute pulmonary hypertension in dogs

It has remained unclear whether endogenous production of nitric oxide (NO) plays an important role in the regulation of physiologically normal pulmonary pressures. Severe alveolar hypoxia is accompanied by decreased pulmonary NO production, which could contribute to the development of hypoxic pulmonary hypertension. On the other hand, pharmacological NO inhibition further augments this hypertensive response.

The aims of the present study were to test: (a) whether NO contributes importantly in the maintenance of baseline pulmonary pressure; and (b) to which degree NO is involved in the pulmonary haemodynamic adjustments to alveolar hypoxia.

In anaesthetized dogs (n=37), the systemic and pulmonary haemodynamic effects of the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 20 mg kg(-1)) and substrate, L-arginine (200-500 mg kg(-1)), were determined at baseline and during alveolar hypoxia. Constant blood flows were accomplished by biventricular bypass, and systemic normoxaemia was maintained by extracorporeal oxygenation.

The primary findings were: (a) L-NAME failed to increase baseline mean pulmonary arterial pressure (10.1 +/- 0.7 vs. 10.5 +/- 0.5 mmHg, P=ns), despite effective NO synthase inhibition as evidenced by robust increases in systemic arterial pressures; (b) L-NAME augmented the pulmonary hypertensive response to alveolar hypoxia (10.2 +/- 0.7 to 19.5 +/- 1.7 with L-NAME vs. 9.9 +/- 1.1 to 15.5 +/- 1.0 mmHg without L-NAME, P<0.05); and (c) L-arginine failed to decrease baseline or elevated pulmonary pressures. Instead, prolonged L-arginine caused increases in pulmonary pressure.

These findings suggest that NO plays no significant role in the tonic physiological control of pulmonary pressure, but endogenous NO becomes an important vasodilatory modulator during elevated pulmonary pressure.