REVERSAL OF PULMONARY VASCULAR REMODELING 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 atria l natriuretic factor (ANF, 800 ng.h(-1).rat(-1)) or a specific inhibit or 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 pro duced by exposure to hypoxia. Methods: Male Wistar rats were kept in a normobaric hypoxic chamber (Fio(2) = 10%) for 7 d. Chronically hypoxi c 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, mi crohaematocrit, and pulmonary vascular remodelling (percentage of thic k walled peripheral vessels) were made in all the rats at different ti me points. Results: The changes in packed cell volume, right ventricul ar hypertrophy, and pulmonary hypertension induced by a 7 d hypoxic ex posure diminished gradually and returned to normal at different time p oints during the 24 d recovery period. In contrast, vascular hypertrop hy in peripheral pulmonary arteries was present after 24 d. There were no significant differences in pulmonary arterial pressure, packed cel l volume, right ventricular hypertrophy and vascular remodelling betwe en ANF NEI, and vehicle treatment groups at either day 8 or day 15. Co nclusions: ANF and NEI treatment had no effect on the reversal of pulm onary hypertension, right ventricular hypertrophy, and vascular remode lling, in contrast to the beneficial actions of ANF and NEI during the development of pulmonary vascular remodelling.