Ca2(+)-induced contraction and hyperreactivity of pulmonary arterial smooth muscle in monocrotaline-treated rats

The mechanism of progressive pulmonary hypertension induced by monocrotaline (MCT) remains controversial. To determine whether or not functional changes in pulmonary arterial smooth muscle contribute to the development of pulmonary hypertension, we examined the reactivity of isolated pulmonary artery segments 7, 14 and 21 days after a single subcutaneous injection of MCT. In Ca2(+)-free buffer, pulmonary arteries from MCT-treated rats contracted when CaCl2 was added without any other stimulation. The pulmonary artery exposed to MCT also exhibited hyperreactivity to KCl and 5-hydroxytryptamine. These functional changes in the pulmonary artery preceded the elevation of right ventricular systolic pressure and right ventricular hypertrophy. The contraction in response to Ca2+ suggests that the pulmonary artery of rats given MCT may be contracted in situ. Vasoconstriction due to these alterations may play an important role in the development of pulmonary hypertension according to this model.