The present study was designed to explore the possible effect Of L-arginine on endogenous hydrogen sulfide/cystathionine-gamma-lyase (H2S/CSE) pathway in the pathogenesis of pulmonary hypertension and pulmonary vascular structural remodeling induced by high pulmonary blood flow. Thirty-two male Sprague-Dawley rats were randomly divided into control group (n = 11) Shunt group (n = 11) and shunt with L-arginine group (n = 10). Rats in the shunt and Shunt with L-arginine group underwent an abdominal aorta-inferior cava vein shunt operation. After 11 weeks of shunting, the plasma level of H,S and lung tissue H,S production rate in the Shunt with L-arginine group were much higher than those in the shunt group (P < 0.01). Meanwhile, the expression of CSE mRNA in the lung tissues of rats in the shunt with L-arginine group was increased significantly (P < 0.01), and in situ hybridization showed that CSE mRNA expression was obviously up-regulated in the smooth muscle cells (SMCs) of the pulmonary arteries of shunted rats treated with L-arginine when compared with shunted rats without the treatment Of L-arginine (P < 0.01). In conclusion, H2S/CSE pathway was up-regulated by L-arginine in pulmonary hypertension induced by high blood flow with the attenuation of pulmonary hypertension and pulmonary vascular structural remodeling. (c) 2006 Elsevier Inc. All rights reserved.