OBJECTIVE To explore the effect and the mechanism of felodipine on pulmonary hypertension. METHODS Adult male Wistar rats were given a single dose of subcutaneous monocrotaline (MCT, 60 mg/kg) to induce the mold of pulmonary hypertension. Felodipine (5 mg/kg) was administered intraperitoneally every day for 4 weeks after MCT injection. The parameters of right ventricular systolic pressure were monitored. The levels of endothelin-like immunoreactivity (ir-ET) and calcitonin gene related peptide (CGRP) in the plasma and the heart and pulmonary tissues were measured by radioimmunoassay and colorimetric analysis. Right ventricular myocardial tissue was studied under electron microscope. RESULTS Continuous injection of felodipine significantly inhibited the progression of pulmonary artery pressure [(44.6 +/- 4.4) mm Hg versus (30.3 +/- 2.1) mm Hg, (18.7 +/- 2.2) mm Hg]. Histological examination revealed that felodipine effectively prevented pulmonary arterial medial thickening. Felodipine significantly increased the level of CGRP in plasma [(84 +/- 19) pg/ml versus 149 +/- 21) pg/ml], pulmonary homogenate [(22 +/- 4) pg/ml versus (29 +/- 3) pg/ml] and myocardial homogenate [(20.9 +/- 1.6) pg/ml versus 27.5 +/- 2.9) pg/ml]. There was no change in the level of ir-ET in the heart and pulmonary tissues. Myocardial damage in the right ventricle was less severe in the felodipine treated group. CONCLUSIONS Long-term use of felodipine was effective in preventing pulmonary hypertension induced by MCT. The underlying mechanism may be partly related to the increase of CGRP as well as the inhibition of Ca(2+) inflow. The results indicate that felodipine may be considered for clinical trials in the treatment of primary pulmonary hypertension.