Abstract
Aim:
To explore the possible role of endogenous hydrogen sulfide (H2S), a novel gasotransmitter, in the pathogenesis of pulmonary vascular structural remodeling (PVSR) induced by high pulmonary blood flow.
Methods:
Thirty-two Sprague-Dawley male rats were randomly divided into sham, shunt, sham+NaHS (a H2S donor) and shunt+NaHS groups. Rats in shunt and shunt+NaHS groups underwent an abdominal aorta-inferior vena cava shunt, and rats in shunt+NaHS and sham+NaHS groups were intraperitoneally injected with NaHS. PVSR was investigated using optical microscope and transmission electron microscope. Lung tissue H2S was evaluated by sulfide-sensitive electrodes. Nitric oxide synthase (NOS), heme oxygenase (HO-1), proliferative cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) activation were analyzed by Western blotting.
Results:
After 11 weeks of shunting, PVSR developed with a decrease in lung tissue H2S production and an increase in nitric oxide (NO). However, lung tissue carbon monoxide (CO) did not change. After the treatment with NaHS for 11 weeks, H2S donor ameliorated PVSR and downregulated PCNA expression and ERK activation with an increase in lung tissue CO production and HO-1 protein expression but a decrease in NO production, NOS activity and eNOS protein expression in shunted rats.
Conclusions:
H2S exerted a regulatory effect on PVSR induced by high pulmonary blood flow. Meanwhile, H2S down-regulated the ERK/MAPK signal pathway, inhibited the NO/NOS pathway and enhanced the CO/HO pathway in rats with high pulmonary blood flow.
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Christou H, Morita T, Hsieh CM, Koike H, Arkonac B, Perrella MA, et al. Prevention of hypoxia-induced pulmonary hypertension by enhancement of endogenous heme oxygenase-1 in the rat. Circ Res 2000; 86: 1224–9.
Wei B, Du JB, Qi JG, Li J, Tang CS . L-Arginine impacts pulmonary vascular structure in rats with an aortocaval shunt. J Surg Res 2002; 108: 20–31.
Shi Y, Du JB, Gong LM, Zeng CM, Tang XY, Tang CS . The regulating effect of heme oxygenase/carbon monoxide on hypoxic pulmonary vascular structural remodeling. Biochem Biophys Res Commun 2003; 306: 523–9.
Zhao W, Zhang J, Lu Y, Wang R . The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J 2001; 20: 6008–16.
Nagahara N, Ito T, Kitamura H, Nishino T . Tissue and subcellular distribution of mercaptopyruvate sulfurtransferase in the rat: confocal laser fluorescence and immunoelectron microscopic studies combined with biochemical analysis. Histochem Cell Biol 1998; 110: 243–50.
Ogasawara Y, Isoda S, Tanabe S . Tissue and subcellular distribution of bound and acid-labile sulfur, and the enzymic capacity for sulfide production in the rat. Biol Pharm Bull 1994; 17: 1535–42.
Yan H, Du J, Tang C . The possible role of hydrogen sulfide on the pathogenesis of spontaneous hypertension in rats. Biochem Biophys Res Commun 2004; 13: 22–7.
Zhong G, Chen F, Cheng Y, Tang C, Du J . The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase. J Hypertens 2003; 21: 1879–85.
Zhang CY, Du JB, Bu DF, Yan H, Tang XY, Tang CS . The regulatory effect of hydrogen sulfide on hypoxic pulmonary hypertension in rats. Biochem Biophys Res Commun 2003; 302: 810–6.
Hui Y, Du J, Tang C, Bin G, Jiang H . Changes in arterial hydrogen sulfide (H2S) content during septic shock and endotoxin shock in rats. J Infect 2003; 47: 155–60.
Geng B, Yang J, Qi Y, Zhao J, Pang Y, Du J, et al. H2S generated by heart in rat and its effects on cardiac function. Biochem Biophys Res Commun 2004; 313: 362–8.
Geng B, Chang L, Pan C, Qi Y, Zhao J, Pang Y, et al. Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol. Biochem Biophys Res Commun 2004; 318: 756–63.
Kimura H . Hydrogen sulfide as a neuromodulator. Mol Neurobiol 2002; 26: 13–9.
Fiorucci S, Antonelli E, Mencarelli A, Orlandi S, Renga B, Rizzo G, et al. The third gas: H(2)S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis. Hepatology 2005; 42: 539–48S.
Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, et al. Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J 2005; 19: 1196–8.
Hosoki R, Matsuki N, Kimura H . The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun 1997; 237: 527–31.
Zhang QY, Du JB, Shi L, Zhang CY, Yan H, Tang CS . Interaction between endogenous nitric oxide and hydrogen sulfide in pathogenesis of hypoxic pulmonary hypertension. Beijing Da Xue Xue Bao 2004; 36: 52–6.
Zhang QY, Du JB, Zhou WJ, Yan H, Tang CS, Zhang CY, et al. Impact of hydrogen sulfide on carbon monoxide oxygenase pathway in the pathogenesis of hypoxic pulmonary hypertension. Biochem Biophys Res Commun 2004; 317: 30–7.
Leffler CW, Parfenova H, Jaggar JH, Wang R . Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation. J Appl Physiol 2006; 100: 1065–76.
Garcia R, Diebold S . Simple, rapid, and effective method of producing aortocaval shunts in the rat. Cardiovasc Res 1990; 24: 430.
Ocampo C, Ingram P, Ilbawi M, Arcilla R, Gupta M . Revisiting the surgical creation of volume load by aorto-caval shunt in rats. Mol Cell Biochem 2003; 251: 139–43.
Bath PJ, Kimpel CH, Roy S, Wagner U . An improved mathematical approach for the assessment of the medical thickness of pulmonary arteries. Pathol Res Pract 1993; 189: 567–76.
Stathopulos PB, Lu X, Shen J, Scott JA, Hammond JR, McCormack DG, et al. Increased l-arginine uptake and inducible nitric oxide synthase activity in aortas of rats with heart failure. Am J Physiol 2001; 280: H859–67.
Morita T, Kourembanas S . Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. J Clin Invest 1995; 96: 2676–82.
Chalmers AH . Simple, sensitive measurement of carbon monoxide in plasma. Clin Chem 1991; 37: 1443–5.
Bongrazio M, Baumann C, Zakrzewicz A, Pries AR, Gaehtgens P . Evidence for modulation of genes involved in vascular adaptation by prolonged exposure of endothelial cells to shear stress. Cardiovasc Res 2000; 47: 384–93.
Thompson K, Rabinovitch M . Exogenous leukocyte and endogenous elastases can mediate mitogenic activity in pulmonary artery smooth muscle cells by release of extracellular matrix-bound basic fibroblast growth factor. J Cell Physiol 1995; 166: 495–505.
Dardik A, Yamashita A, Aziz F, Asada H, Sumpio BE . Shear stress-stimulated endothelial cells induce smooth muscle cell chemotaxis via platelet-derived growth factor-BB and interleukin-1alpha. J Vasc Surg 2005; 41: 321–31.
Dumitrascu R, Weissmann N, Ghofrani HA, Dony E, Beuerlein K, Schmidt H, et al. Activation of soluble guanylate cyclase reverses experimental pulmonary hypertension and vascular remodeling. Circulation 2006 [ Epub ahead of print].
Hartsfield CL, McMurtry IF, Ivy DD, Morris KG, Vidmar S, Rodman DM, et al. Cardioprotective and vasomotor effects of HO activity during acute and chronic hypoxia. Am J Physiol Heart Circ Physiol 2004; 287: H2009–15.
Du J, Hui Y, Cheung Y, Bin G, Jiang H, Chen X, et al. The possible role of hydrogen sulfide as a smooth muscle cell proliferation inhibitor in rat cultured cells. Heart Vessels 2004; 19: 75–80.
Eto K, Ogasawara M, Umemura K, Nagai Y, Kimura H . Hydrogen sulfide is produced in response to neuronal excitation. J Neuro Sci 2002a; 22: 3386–91.
Yang G, Cao K, Wu L, Wang R . Cystathionine gamma-lyase overexpression inhibits cell proliferation via a H2S-dependent modulation of ERK1/2 phosphorylation and p21Cip/WAK-1. J Biol Chem 2004; 279: 49199–205.
Blenis J . Signal transduction via the MAP kinases: proceed at your own RSK. Proc Natl Acad Sci USA 1993; 90: 5889–92.
Shi Y, Du JB, Guo ZL, Zeng CM, Tang CS . Interaction between endogenous nitric oxide and carbon monoxide in the pathogenesis of hypoxic pulmonary hypertension. Chin Sci Bull 2003; 48: 86–90.
Beauchamp RO, Bus JS, Popp JA, Boreiko CJ, Andjelkovich DA . A critical review of the literature on hydrogen sulfide toxicity. Crit Rev Toxicol 1984; 13: 25–97.
Wang R . Resurgence of carbon monoxide: an endogenous gaseous vasorelaxing factor. Can J Physiol Pharmacol 1998; 76: 1–15.
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Project supported by the National Science Fund for Distinguished Young Scholars (No 30425010), the State Major Basic Research Project of China and the Natural Science Foundation of Beijing, China (No 7052043).
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Li, Xh., Du, Jb., Bu, Df. et al. Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats. Acta Pharmacol Sin 27, 971–980 (2006). https://doi.org/10.1111/j.1745-7254.2006.00353.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00353.x
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