Chronic inhaled nitric oxide: effects on pulmonary vascular endothelial function and pathology in hypoxic and normoxic rats. Roos, Christine M., Deborah U. Frank, Chun Xue, Roger A. Johns, George F. Rich. Departments of Anesthesiology and Biomedical Engineering, University of Virginia Health Sciences Center, Charlottesville, VA 22908
APStracts 2:0397A, 1995.
Nitric oxide (NO) is a potent endogenous vasodilator produced in endothelial cells. Inhaled NO selectively vasodilates the pulmonary circulation. We determined the effects of chronic inhaled NO on hypoxic pulmonary vascular remodeling and endothelium NO-dependent and independent vasodilation during normoxic and hypoxic conditions in rats. Rats were exposed to three weeks of normoxia (N), normoxia + 20 ppm inhaled NO (N+NO), chronic hypoxia with 10% normobaric oxygen (CH), or CH and 20 ppm inhaled NO (CH +NO). Inhaled NO decreased the number of muscular pulmonary arteries, the medial smooth muscle thickness and the right ventricular hypertrophy associated with chronic hypoxia, but had no effect on these parameters in normoxic rats. All groups were evaluated with isolated perfused lungs. The pulmonary artery pressure was increased the same in the CH and CH+NO rats compared to N. Inhibition of nitric oxide synthase with Nw -nitro-L-arginine methyl ester (L-NAME) caused greater pulmonary vasoconstriction in CH (19.2+/-3.7 mmHg) vs N (7.8+/-3.0 mmHg) and less in CH+NO (9.1+/-0.8 mmHg) vs CH rats. Bradykinin (3 [mu]g) caused greater vasodilation in CH (76+/-12%) vs N (29+/-5%) but significantly less in CH+NO (41+/-11%) vs CH rats. Vasodilation with acute inhaled NO (40 ppm) was no different in CH vs N rats but was lower in CH+NO (19+/-5%) vs CH (34+/-6%) rats. This study demonstrates that chronic inhaled NO attenuates hypoxic pulmonary vascular remodeling. Furthermore, these results suggest that chronic inhaled NO decreases endothelium NO-dependent and independent vasodilation. 

Received 23 May 1995; accepted in final form 1 September 1995.
APS Manuscript Number A541-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.