Impact of hydrogen sulfide, a novel gaseous signal molecule on nitric oxide/nitric oxide synthase pathway in left-to-right shunt: experiment with rats

Abstract

To explore the impact of endogenous hydrogen sulfide (H(2)S), a novel gaseous signal molecule, on the nitric oxide (NO)/nitric oxide synthase (NOS) pathway in left-to-right shunt. Thirty-two male SD rats were randomly divided into 4 equal groups: shunt group undergoing abdominal aorta-inferior vena cava puncture so as to establish model of left-to-right shunt; shunt + PPG group undergoing abdominal aorta-inferior vena cava puncture so as to establish model of left-to-right shunt and then intraperitoneal injection of propargylglycine (PPG), an inhibitor of cystathionine-gamma-lyase: sham group undergoing sham operation; and sham + PPG group undergoing sham operation and then intraperitoneal injection of PPG. Four weeks later, right cardiac catheterization was conducted to measure the mean pulmonary artery pressure (MPAP). Then the rats were killed and their lung tissues and samples of plasma were collected. The contents of H(2)S, nitric oxide (NO), and nitrogen oxide synthase (NOS) activity, and the content of plasma NO were calculated. Western blotting was used to detect the endothelial nitric oxide synthase (eNOS) protein in the lung tissues. The correlation of MPAP with lung H(2)S and NO was analyzed. The MPAP of the shunt group was not significantly different from that of the sham group, and the MPAP of the shunt + PPG group was significantly higher then those of the shunt group and sham group by 15.82% and 20.55% respectively (both P < 0.05). The content of lung tissue H(2)S of the shunt group was 37.56 +/- 2.13 micromol/mg, significantly higher than that of the shunt group (14.35 +/- 1.76, P < 0.05), the content of lung tissue H(2)S of the shunt + PPG group was 28.76 +/- 2.24 micromol/mg, significantly lower than that of the shunt group (P < 0.05). The lung tissue NO content of the shunt group was 38.48 micro +/- 6.53 micromol/microg, significantly higher than that of the sham group (31.78 +/- 6.51 micromol/microg). The NOS activity of the shunt group was 15.12 +/- 2.44 U/mg protein, significantly higher than that of the sham group (12.00 +/- 1.40 U/mg protein, P < 0.05). The lung eNOS content of the shunt group was significantly higher than that of the sham group (P < 0.05). The plasma NO content of the shunt group was 23.18 +/- 3.56 micromol/L, significantly higher than that of the sham group (17.94 +/- 3.39 micromol/L, P < 0.05). The lung tissues NO and NOS activity, and plasma NO of the shunt + PPG group were 46.04 +/- 5.95 micromol/microg, 20.89 +/- 3.94 U/mg protein, and 27.79 +/- 4.82 micromol/L respectively, all significantly higher than those of the shunt group (38.48 +/- 6.53 micromol/microg, 15.12 +/- 2.44 U/mg protein, and 23.18 +/- 3.56 micromol/L, all P < 0.05). The eNOS content of the shunt + PPG group was significantly higher than that of the shunt group (P < 0.05). The lung H(2)S content was negatively correlated with the MPAP and lung NO content (r = -0.705, P = 0.005; and r = -0.645, P = 0.013). Endogenous H(2)S may play a regulatory role in the pulmonary artery pressure of left-to-right shunt through inhibiting NO/NOS pathway.