Down-Regulation of Endogenous Hydrogen Sulfide Pathway in Pulmonary Hypertension and Pulmonary Vascular Structural Remodeling Induced by High Pulmonary Blood Flow in Rats

Abstract

Background The mechanisms responsible for the development of pulmonary hypertension (PH) and pulmonary vascular structural remodeling induced by high pulmonary blood flow are not fully understood. The present study was designed to explore the possible changes in endogenous hydrogen sulfide (H₂S), a novel gasotransmitter, on the pathogenesis of PH and pulmonary vascular structural remodeling induced by high pulmonary blood flow. Methods and Results Twenty-two male Sprague-Dawley rats were randomly divided into a shunting group (n=11) and control group (n=11). Rats in the shunting group underwent an abdominal aorta-inferior cava vein shunting operation. After 11 weeks of shunting, the plasma level of H₂S and lung tissue H₂S producing rate were much lower than those of the control group (p<0.01). In situ hybridization analysis showed that the expression of cystathionine γ-lyase (CSE) mRNA was down-regulated in the pulmonary arteries of the shunting rats compared with the control group (p<0.01), and competitive quantitative reverse transcription-polymerase chain reaction showed that the relative amount of CSEmRNA in lung tissue was decreased significantly (p<0.01). Conclusions The endogenous H₂S pathway is down-regulated in PH and pulmonary vascular structural remodeling is induced by high pulmonary blood flow. (Circ J 2005; 69: 1418 - 1424)