Angiotensin-converting enzyme activity is increased in lungs of rats with pulmonary hypoplasia and congenital diaphragmatic hernia.

Abstract

Lung hypoplasia (LH) and pulmonary hypertension are responsible for the high mortality rate in congenital diaphragmatic hernia (CDH) patients. Angiotensin-converting enzyme (ACE) plays a role in the regulation of pulmonary vascular resistance in the postnatal period and might be involved in the development of pulmonary hypertension of the newborn. A study was made of the development of ACE activity spectrophotometrically in a rat model of LH and CDH. It was previously shown that the lungs in this model are hypoplastic and the muscularization of the pulmonary vascular bed is increased. CDH was induced in fetal rats by oral administration of 115 mg/kg Nitrofen to the mother on day 10.5 of pregnancy. Fetuses were delivered by hysterotomy on days 19, 20, 21, and 22. Nitrofen-exposed rats showed significantly lower lung weights and not statistically significant lower total ACE activities than in controls. ACE activity expressed per milligram lung wet weight and per milligram protein was significantly increased compared to controls. ACE converts angiotensin I to the vasoconstrictor angiotensin II, and it inactivates the vasodilator bradykinin. Increased ACE activity may therefore contribute to pulmonary hypertension. Whether ACE and angiotensin II levels are increased in human newborns with a diaphragmatic defect and whether they contribute to the development of persistent pulmonary hypertension has not been studied up till now.