Reversal of pulmonary vascular remodelling following hypoxic exposure: no effect of infusion of atrial natriuretic factor and neutral endopeptidase inhibitor

Objective: The aim was to investigate whether infusion of either atrial natriuretic factor (ANF, 800 ng·h−1·rat−1) or a specific inhibitor of neutral endopeptidase 24.11 (NEI, UK 73,967, 5.4 mg·kg−1·d−1) can influence the reversal of the pulmonary vascular remodelling produced by exposure to hypoxia. Methods: Male Wistar rats were kept in a normobaric hypoxic chamber (Fio2=10%) for 7 d. Chronically hypoxic rats were then treated with intravenous infusion of vehicle, ANF, or NEI by osmotic minipumps. Measurements of pulmonary artery pressure, systemic blood pressure, heart rate, right ventricular hypertrophy, microhaematocrit, and pulmonary vascular remodelling (percentage of thick walled peripheral vessels) were made in all the rats at different time points. Results: The changes in packed cell volume, right ventricular hypertrophy, and pulmonary hypertension induced by a 7 d hypoxic exposure diminished gradually and returned to normal at different time points during the 24 d recovery period. In contrast, vascular hypertrophy in peripheral pulmonary arteries was present after 24 d. There were no significant differences in pulmonary arterial pressure, packed cell volume, right ventricular hypertrophy and vascular remodelling between ANF, NEI, and vehicle treatment groups at either day 8 or day 15. Conclusions: ANF and NEI treatment had no effect on the reversal of pulmonary hypertension, right ventricular hypertrophy, and vascular remodelling, in contrast to the beneficial actions of ANF and NEI during the development of pulmonary vascular remodelling. Cardiovascular Research 1994;28:519-523