The modulating effect of L-arginine on collagen metabolism of pulmonary artery in pulmonary hypertension induced by a left-to-right shunt

Abstract

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.

Method: 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).

Conclusion: 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.