[The effect and mechanism of felodipine on monocrotaline induced pulmonary hypertension in rats].
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.
Zeng
Zhiyu
Z
Cardiovascular Disease Research Institute of Guangxi Medical University, Nanning 530021, China.
Huang
Hai
H
Li
Xingsan
X
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016232:Endothelins / Q000097:blood; D015736:Felodipine / Q000494:pharmacology / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D009206:Myocardium / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013599:Systole / Q000187:drug effects
D002121:Calcium Channel Blockers; D016232:Endothelins; D016686:Monocrotaline; D015740:Calcitonin Gene-Related Peptide; D015736:Felodipine