The modulating effect of L-arginine on collagen metabolism of pulmonary artery in pulmonary hypertension induced by a left-to-right shunt.
OBJECTIVE
To explore the modulating effect of L-arginine on collagen metabolism of pulmonary artery in rats with high pulmonary blood flow-induced pulmonary hypertension and its molecular mechanism.


METHODS
Eighteen rats were randomly divided into 3 groups of 6 rats: shunt group (pulmonary hypertension was established with an abdominal aorta and inferior vena cava shunting), shunt + L-Arg group (L-arginine, 1 g x kg(-1) x d(-1) was given into the stomachs of rats for weeks after shunting), and control group. After 11 weeks of experiment, the pulmonary hemodynamics were studied, the contents of collagen I and collagen III expressions were detected by immunohistochemical assay. The expressions of procollagen I mRNA, procollagen III mRNA, TIMP-1 mRNA and MMP-1 mRNA were detected by in situ hybridization.


RESULTS
After 11 weeks of experiment, the mean pulmonary artery pressure (MPAP) in shunt group was 23.0 mm Hg +/- 0.9 mm Hg, higher than that in shunt + L-Arg group (18.0 mm Hg +/- 1.8 mm Hg, P < 0.01) and that in control group (15.7 mm Hg +/- 1.1 mm Hg, P < 0.01). The expressing integral scores of collagen I and collagen III, the expression of procollagen I mRNA, Procollagen III mRNA, TIMP-1 mRNA, MMP-1 mRNA and the ratio of TIMP-1/MMP-1 were significantly higher in the shunt group than in the other 2 groups (P < 0.01 or P < 0.05).


CONCLUSIONS
L-arginine reduces the synthesis of extracellular matrix-collagen and increases its degradation. Thus L-arginine has important modulating effects on pulmonary hypertension and pulmonary vascular remodeling induced by high pulmonary blood flow.
Wei
Bing
B
Department of Pediatrics, First Hospital, Peking University, Beijing 100034, China.
Du
Junbao
J
Li
Jian
J
Qi
Jianguang
J
Tang
Chaoshu
C
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000098:blood supply; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D001120:Arginine; D020781:Matrix Metalloproteinase 1