Lung vessel leak precedes right ventricular hypertrophy in monocrotaline-treated rats

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Abstract
Monocrotaline induces microvascular leak and pulmonary hypertension in rats. We have hypothesized that the leak is related in some way to the pulmonary hypertension and precedes it. In rats given 40 mg monocrotaline/kg body wt subcutaneously, lung wet weight-to-dry weight ratios and lung albumin content began to increase within the first 3 days and became maximal at 1 wk. Alveolar lavage fluid showed little or no increase in protein. Right ventricular hypertrophy increased progressively from 2 through 3 wk. An increase in lung dry weight paralleled the right ventricular hypertrophy. The amount of blood retained in the lung did not account for the increased lung water, albumin, or weight. We considered that microvascular leak without leak into the alveolar space preceded pulmonary hypertension, right ventricular hypertrophy, and increased lung dry weight. In rats not given monocrotaline but exposed for 3 wk to hypobaric hypoxia, lung albumin, lung dry weight, and right ventricular weight increased. Increased lung dry weight probably reflects hyperplasia of lung cells. If so, an association of microvascular leak, lung cell hyperplasia, and right ventricular hypertrophy may occur in both monocrotaline- and hypoxia-induced pulmonary hypertension.