Relationship between Chronic Hypoxia and In Vitro Pulmonary Relaxation Mediated by Endothelium-Derived Relaxing Factors in Human Chronic Obstructive Lung Disease

Abstract

Endothelium-derived relaxing factors (EDRF) are paracrine vasodilator sub stances released by endothelial cells. There is compelling evidence to suggest that EDRF may play an important role in the modulation of vascular tone in the systemic circulation. However, the role of EDRF-mediated pulmonary relaxa tion in chronic lung disease is unknown. The authors have, therefore, investigated endothelium-dependent relaxation of isolated pulmonary arteries (PAs) obtained from 18 patients undergoing heart-lung transplantation for end-stage chronic hypoxic cor pulmonale (HCP). Control PAs were obtained from 10 patients, none of whom had evidence of HCP, and who underwent lobectomy for lung carcinoma. All vascular rings were studied immediately after lung excision. PA rings from control patients dose-dependently relaxed to cumulative doses of acetylcholine (ACh, 10-10 to 10 -5 M), achieving a maximal relaxation of 73.2±4.4% from precontraction to phenylephrine. By contrast, PA rings from HCP patients achieved only 42.1 ±6.7% of maximal relaxation (p<0.01). Sodium nitroprus side (10-4 M) relaxed all PA rings, with and without endothelium (carefully re moved before study), obtained from both control and HCP patients. The endothelium-dependent maximal relaxation to ACh was positively related to pretransplant values of PaO2 (r = 0.59; p< 0.01), but no relationship was found with either PaCO2 (r = -0.41) or FEV1 (r = -0.14). The authors conclude that pulmonary relaxation mediated by EDRF is im paired in human HCP and suggest that such impairment may be related to severity of the preexisting chronic hypoxemia.