We have investigated 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 subcutaneous injection of the pyrrolizidine alkaloid monocrotaline. Thirty-six young female Wistar rats were divided into a test group of 27 animals and a control group of nine animals. Each test rat was given a single subcutaneous injection of monocrotaline (60 mg/kg body weight). On the first, third, fifth, seventh, tenth, twelfth, fourteenth, seventeenth, and twenty-second days after the injection of monocrotaline the mean right ventricular systolic blood pressure was measured in one control and three test rats. The animals were then killed and we measured the specific activity of ACE in serum and lung homogenate. We also evaluated muscularisation of pulmonary arterioles, medial hypertrophy of muscular pulmonary arteries, and right ventricular hypertrophy. The sequence of changes was as follows: muscularisation of pulmonary arterioles and medial hypertrophy of muscular pulmonary arteries were apparent seven 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. If is concluded that 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.Monocrotaline is a pyrrolizidine alkaloid present in the seeds and foliage of the leguminous plant Crotalaria spectabilis. The administration of this alkaloid to rats produces pulmonary hypertension, hypertensive pulmonary vascular disease and right ventricular hypertrophy.1 The pulmonary vascular lesions comprise thickening of the pulmonary trunk, medial hypertrophy of muscular pulmonary arteries, and muscularisation of pulmonary arterioles. In about one-third of rats there is also an acute necrotising pulmonary arteritis. The

Responses of plasma renin activity, plasma aldosterone, plasma cortisol, and plasma electrolyte concentration and urinary electrolyte and aldosterone excretion were studied in four men during hypoxic decompression to a stimulated altitude of 4,760 m in a pressure chamber. Three of the four subjects developed significant acute mountain sickness. Plasma sodium and potassium concentrations were unchanged. No significant change in plasma renin activity was observed, but values tended to fall. Plasma aldosterone concentration was depressed while plasma cortisol was elevated and diurnal variation lost. Urinary sodium excretion was unchanged, but urinary potassium and aldosterone excretion were decreased. The decrease in plasma and urinary aldosterone and urinary potassium in the absence of change in plasma renin activity or plasma potassium is of uncertain origin. It is unlikely to be due to a decrease in adrenocorticotropin secretion since plasma cortisol rose during the same time. None of the changes could be causally implicated in the development of acute mountain sickness although the increase in plasma cortisol was greatest in the most ill.

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We have studied serum and lung tissue angiotensin converting enzyme (ACE) activity in female Wistar rats with pulmonary hypertension induced by two different methods. Chronic pulmonary hypertension was produced in one group of 10 rats (CH) by confinement in a hypobaric chamber (380 mmHg) for three weeks, and in another group of 10 rats (M) by a single subcutaneous injection of monocrotaline (60 mg/kg body weight). In these two groups of test rats and in 20 untreated controls (C), we evaluated right ventricular mean systolic blood pressure (Prvs mmHg), right ventricular hypertrophy, and serum ACE (n mol/ml/min). In pancreas, adrenal, liver, and kidney.3 However, it has been calculated that most of the ACE activity in the body occurs in the lungs4 where the enzyme has been localised on the luminal surface of pulmonary endothelial cells in relation to the plasma membrane.5 It has been shown that the pulmonary conversion of angiotensin I to angiotensin II is a function of the vascular surface area and the transit time of blood through the lung.6 Accordingly, it might be expected that diffuse lung disease and pulmonary hypertension in particular would be associated with alterations of lung ACE activity. However, although there have been a few studies of lung ACE activity in acute hypoxia,7 8 chronic hypoxia,9 and acute lung injury,10 11 there has been only one study specifically related to pulmonary hypertension.'2The purpose of this paper is to describe the effect of pulmonary hypertension on lung ACE activity. We induced chronic pulmonary hypertension in one 198 on 8 May 2018 by guest. Protected by copyright.

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