Transpulmonary angiotensin II formation and pulmonary haemodynamics in stable hypoxic lung disease: the effect of captopril.
The effect of chronic hypoxic lung disease on the activity of the renin-angiotensin (RA) system and the role the RA system plays in the pulmonary vascular changes that accompany hypoxia remain controversial. We have measured transpulmonary generation of angiotensin II (A II) and pulmonary haemodynamics in nine patients with airflow obstruction (mean FEV1 = 0.741) and arterial hypoxaemia (mean PaO2 = 8.4 Pa) before and after captopril. In each patient pulmonary artery pressure, cardiac output, systemic arterial pressure, arterial and mixed venous blood gas tensions and arterial and mixed venous A II were measured at rest and at intervals for a total of 3 h after 25 mg captopril orally. The patients had moderate pulmonary hypertension (mean = 29 mmHg) and slightly raised A II levels (mean = 47.2 pg ml-1) but no step-up in A II levels across the lung. After captopril, both arterial and mixed venous A II levels fell by, on average 80% (SEM 2%), but the transpulmonary gradient for A II remained unchanged for each subject. The systemic arterial pressure fell by an average 18% (SEM 5%). In seven patients pulmonary vascular resistance fell (mean = 31%, SEM 6%) and in two patients it rose. There was no significant change in blood gas tensions. These findings suggest that patients with chronic hypoxic lung disease have decreased conversion of A I to A II in the lung but stimulation of the extra-pulmonary renin-angiotensin system. ACE inhibition appears to cause a fall in PVR in most patients with severe chronic airflow obstruction without deterioration in gas exchange.