L-Arginine Impacts Pulmonary Vascular Structure in Rats with an Aortocaval Shunt

Abstract

Background. The present study was designed to explore the therapeutic effect of l-arginine on the proliferation and apoptosis of pulmonary artery smooth muscle cells (SMCs) in high pulmonary blood flow-induced pulmonary hypertension and therefore to provide a basis for the mechanism by which l-arginine regulated pulmonary hypertension. Materials and methods. Twenty-one male SD rats were randomly divided into shunting group, shunting with l-arginine group, and control group. Abdominal aorta and inferior vena cava shunting was produced in rats of the shunting group and the shunting with l-arginine group. Pulmonary artery mean pressure (mPAP) and pulmonary vascular microstructure were analyzed. Immunohistochemistry for proliferative cell nuclear antigen (PCNA) and Fas expressions and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) were used to detect cell proliferation and apoptosis, respectively. Results. mPAP, RV/BW, and RV/LV + S were significantly increased in shunted rats compared to normal controls ( P < 0.01, respectively). Pulmonary vascular structural remodeling developed in shunted rats. Proliferative index (PI), apoptotic index (AI), and the ratio of PI/AI of pulmonary artery SMCs in the rats of shunting group were elevated obviously ( P < 0.01). Meanwhile, the expressing integral score of Fas was elevated in the shunting group ( P < 0.01). However, l-arginine significantly attenuated pulmonary artery pressure and ameliorated pulmonary vascular structural remodeling. Also, it reduced PI and again augmented AI of pulmonary artery SMCs. The ratio of PI/AI was significantly reduced ( P < 0.01). The expressing integral score of Fas was again augmented by l-arginine ( P < 0.01). Conclusion. l-Arginine could inhibit proliferation and promote apoptosis of pulmonary artery SMCs in shunted rats.