Angiotensin converting enzyme activity and evolution of pulmonary vascular disease in rats with monocrotaline pulmonary hypertension.

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Abstract
The role of angiotensin converting enzyme (ACE) in the development of pulmonary hypertension, right ventricular hypertrophy and pulmonary vascular disease in rats given a single s.c. injection of the pyrrolizidine alkaloid monocrotaline [isolated from Crotalaria spectabilis] was investigated. Thirty-six young female Wistar rats were divided into a test group of 27 animals and a control group of 9 animals. Each test rat was given a single s.c. injection of monocrotaline (60 mg/kg body wt). On the 1st, 3rd, 5th, 7th, 12th, 14th, 17th and 22nd day after the injection of monocrotaline the mean right ventricular systolic blood pressure was measured in 1 control and 3 test rats. The animals were then killed and the specific activity of ACE in serum and lung homogenate was measured. Muscularization of pulmonary arterioles, medial hypertrophy of muscular pulmonary arteries and right ventricular hypertrophy were evaluated. The sequence of changes was as follows: muscularization of pulmonary arterioles and medial hypertrophy of muscular pulmonary arteries were apparent 7 days after administration of monocrotaline; pulmonary hypertension and reduced lung ACE activity occurred after 10 days; right ventricular hypertrophy was detected after 12 days. Serum ACE activity was unchanged. The reduction in lung ACE activity is a result rather than a cause of the pulmonary hypertension. This reduction in lung ACE activity may be a protective mechanism designed to limit the elevation of the pulmonary arterial pressure.