Effect of L-Arginine on Collagen of High Flow-Induced Pulmonary Arterial Remodeling

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Background Pulmonary hypertension (PH) is a common complication of congenital heart disease and pulmonary vascular structural remodeling due to the high pulmonary blood flow is considered as the key pathologic process. In the present study the effects of L-arginine on the collagen metabolism of pulmonary arteries in rats with high pulmonary blood flow-induced PH were investigated to elucidate its mechanism. Methods and Results The rat model of PH was established with an abdominal aorta and inferior vena cava shunt. L-arginine (1g/kg per day) was given directly into the stomachs of the rats with the shunt (L-arginine+shunt group) and 11 weeks later, the pulmonary hemodynamics were studied. Collagen I and collagen III expressions were detected by immunohistochemical assay. The expressions of procollagen I mRNA, procollagen III mRNA, the tissue inhibitor of metalloproteinase-l mRNA and the matrix metalloproteinase-l mRNA were detected by in situ hybridization. The expressions of pulmonary artery collagen I, collagen III, procollagen I mRNA and procollagen III mRNA in the shunt rats were obviously elevated compared with the control rats (p<0.01). The positive signals were mainly located in the media and adventitia of median and small pulmonary arteries. The expressions of the pulmonary artery tissue inhibitor of metalloproteinase-l mRNA, metalloproteinase-lmRNA and the ratio of tissue inhibitor of metalloproteinase-l/metalloproteinase-l were elevated in the shunt rats (p<0.01). However, the expressions of pulmonary artery collagen I, collagen III, procollagen I mRNA and procollagen III mRNA were significantly reduced in the shunt rats of the L-arginine group (p<0.01). L-arginine also downregulated the expressions of tissue inhibitor of metalloproteinase-l mRNA and metalloproteinase-l mRNA, as well as the ratio of tissue inhibitor of metalloproteinase-l/metalloproteinase-l (p<0.05). Conclusions L-arginine can reduce the synthesis of extracellular matrix-collagen and increase its degradation, thus having an important modulating effect on pulmonary vascular matrix remodeling induced by high pulmonary blood flow.
社団法人日本循環器学会の論文
2005-04-20

Effect of L-Arginine on Collagen of High Flow-Induced Pulmonary Arterial Remodeling

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