Nomega-Nitro-L-Arginine Benzyl Ester Enhances Pulmonary Vasopressor Responses to Hypoxia and to Angiotensin II.
The effects of Nomega-nitro-L-arginine benzyl ester (L-NABE), an inhibitor of nitric oxide (NO) synthase, were investigated on pulmonary arterial responses during baseline or low tone conditions and during elevated tone conditions induced by ventilatory hypoxia or by AII in the isolated blood-perfused rat lung. We also tested the influence L-NABE on the vasodilator responses to acetylcholine (ACh) and nitroglycerin (GTN) during elevated pulmonary arterial tone conditions. Under baseline conditions, L-NABE in doses of 10--1000 &mgr;g, induced small increases in pulmonary arterial perfusion pressure that were significant for the higher doses studied. Ventilation with an hypoxic gas mixture or administration of AII significantly increased pulmonary arterial perfusion pressure and the responses were reproducible with respect to time. Following administration of L-NABE, the pulmonary arterial responses to hypoxic ventilation (HPV) were significantly enhanced, and L-NABE significantly enhanced the pulmonary arterial pressor responses to angiotensin II. During elevated pulmonary arterial tone conditions induced with hypoxic ventilation, L-NABE inhibited the vasodilator responses to acetylcholine (ACh); however, the vasodilator responses to nitroglycerin (GTN) were not altered. The small effect of L-NABE on baseline pulmonary arterial pressure in the isolated blood-perfused rat lung suggests that NO plays only a small role in maintaining pulmonary vascular tone at low resting levels. However, the augmentation of the pressor responses by L-NABE during HPV and to AII suggests that NO plays an important role in modulating these pulmonary pressor responses during elevated tone conditions. Additionally, the inhibition of pulmonary vasodilator response to ACh supports the hypothesis that NO release plays a major role in mediating vasodilator responses to endothelial-dependent agents such as ACh, but not to endothelial-independent agents such as GTN. In conclusion, these data suggest that NO release is more important under stimulated conditions than under basal conditions.
Nossaman
Bobby Dean
BD
Departments of Anesthesiology and Pharmacology, Tulane University Medical School, New Orleans, USA.
Kaye
Alan David
AD
Gitlin
Melvin Charles
MC
Kadowitz
Philip J.
PJ
Feng
Chang Jian
CJ