Abstract
Aim:
To compare the vasorelaxing effects of hydrogen sulfide (H2S) on isolated aortic and pulmonary artery rings and to determine their action mechanisms.
Methods:
H2S-induced vasorelaxation of isolated rat aortic versus pulmonary artery rings under 95% O2 and 5% CO2 was analyzed. The expression of cystathinonine gamma-lyase (CSE), cystathionine beta synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST), SUR2B and Kir6.1 was examined.
Results:
NaHS caused vasorelaxation of rat aortic and pulmonary artery rings in a dose-dependent manner. NaHS dilated aortic rings to a greater extent (16.4%, 38.4%, 64.1%, 84.3%, and 95.9% at concentrations of 50, 100, 200, 500, and 1000 μmol/L, respectively) than pulmonary artery rings (10.1%, 22.2%, 50.6%, 73.6%, and 84.6% at concentrations of 50, 100, 200, 500 and 1000 μmol/L, respectively). The EC50 of the vasorelaxant effect for aortic rings was 152.17 μmol/L, whereas the EC50 for pulmonary artery rings was 233.65 μmol/L. The vasorelaxing effect of H2S was markedly blocked b y cellular and mitochondrial membrane KATP channel blockers in aortic rings (P<0.01). In contrast, only the cellular membrane KATP channel blocker inhibited H2S-induced vasorelaxation in pulmonary artery rings. SUR2B mRNA and protein expression was higher in aortic rings than in pulmonary artery rings. Cystathinonine gamma-lyase (CSE) but not cystathionine beta synthase (CBS) expression in aortic rings was higher than in pulmonary artery rings. 3-Mercapto pyruvate sulfurtransferase (3MST) mRNA was lower in aortic rings than in pulmonary artery rings.
Conclusion:
The vasorelaxing effect of H2S on isolated aortic rings was more pronounced than the effect on pulmonary artery rings at specific concentrations, which might be associated with increased expression of the KATP channel subunit SUR2B.
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References
Aaronson PI, Robertson TP, Knock GA, Becker S, Lewis TH, Snetkov V, et al. Hypoxic pulmonary vasoconstriction: mechanisms and controversies. J Physiol 2006; 570: 53–8.
Gray GA, Webb DJ . The endothelin system and its potential as a therapeutic target in cardiovascular disease. Pharmacol Ther 1996; 72: 109–48.
Sata M, Fukuda D . Crucial role of renin-angiotensin system in the pathogenesis of atherosclerosis. J Med Invest 2010; 57: 12–25.
Lipworth BJ, Dagg KD . Vasoconstrictor effects of angiotensin II on the pulmonary vascular bed. Chest 1994; 105: 1360–4.
Olson KR, Dombkowski RA, Russell MJ, Doellman MM, Head SK, Whitfield NL, et al. Hydrogen sulfide as an oxygen sensor/transducer in vertebrate hypoxic vasoconstriction and hypoxic vasodilation. J Exp Biol 2006; 209: 4011–23.
Tang C, Li XH, Du JB . Hydrogen sulfide as a new endogenous gaseous transmitter in the cardiovascular system. Curr Vasc Pharmacol 2006; 4: 17–22.
Chen CQ, Xin H, Zhu YZ . Hydrogen sulfide: third gaseous transmitter, but with great pharmacological potential. Acta Pharmacol Sin 2007; 28: 1709–16.
Bhatia M . Hydrogen sulfide as a vasodilator. IUBMB Life 2005; 57: 603–6.
O'Sullivan SE . What is the significance of vascular hydrogen sulphide (H2S)? Br J Pharmacol 2006; 149: 609–10.
Bełtowski J . Hydrogen sulfide as a biologically active mediator in the cardiovascular system. Postepy Hig Med Dosw 2004; 58: 285–91.
Łowicka E, Bełtowski J . Hydrogen sulfide (H2S)-the third gas of interest for pharmacologists. Pharmacol Rep 2007; 59: 4–24.
Szabó C . Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov 2007; 6: 917–35.
Shibuya N, Mikami Y, Kimura Y, Nagahara N, Kimura H . Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide. J Biochem 2009; 146: 623–6.
Olson KR, Whitfield NL, Bearden SE . St Leger J, Nilson E, Gao Y, et al. Hypoxic pulmonary vasodilation: a paradigm shift with a hydrogen sulfide mechanism. Am J Physiol Regul Integr Comp Physiol 2010; 298: R51–60.
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.
Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, et al. H2S as a Physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science 2008; 322: 587–90.
Yeager ME, Halley GR, Golpon HA, Voelkel NF, Tuder RM . Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension. Circ Res 2001; 88: 2–11.
Zhu P, Huang L, Ge X, Yan F, Wu R, Ao Q . Transdifferentiation of pulmonary arteriolar endothelial cells into smooth muscle-like cells regulated by myocardin involved in hypoxia-induced pulmonary vascular remodelling. Int J Exp Pathol 2006; 87: 463–74.
Chen YH, Wu R, Geng B, Qi YF, Wang PP, Yao WZ, et al. Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat model of asthma. Cytokine 2009; 45: 117–23.
Patacchini R, Santicioli P, Giuliani S, Maggi CA . Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in rat detrusor muscle. Eur J Pharmacol 2005; 509: 171–7.
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.
Geng B, Yang J, Qi Y, Zhao J, Pang Y, Du J, Tang C . H2S generated by heart in rat and its effects on cardiac function. Biochem Biophys Res Commun 2004; 313: 362–8.
Su YW, Liang C, Jin HF, Tang XY, Han W, Chai LJ, et al. Hydrogen sulfide regulates cardiac function and structure in adriamycin-induced cardiomyopathy. Circ J 2009; 73: 741–9.
Li L, Hsu A, Moore PK . Actions and interactions of nitric oxide, carbon monoxide and hydrogen sulphide in the cardiovascular system and in inflammation — a tale of three gases. Pharmacol Ther 2009; 123: 386–400.
Wang YF, Shi L, Du JB . Impact of L-arginine on hydrogen sulfide/cystathionine-γ-lyase pathway in rats with high blood flow-induced pulmonary hypertension. Biochem Biophys Res Commun 2006; 345: 851–7.
Yan H, Du JB, Tang CS . The possible role of hydrogen sulfide on the pathogenesis of spontaneous hypertension in rats. Biochem Biophys Res Commun 2004; 313: 22–7.
Mancardi D, Penna C, Merlino A . Del Soldato P, Wink DA, Pagliaro P . Physiological and pharmacological features of the novel gasotransmitter: Hydrogen sulfide. Biochim Biophys Acta 2009; 1787: 864–72.
Sun YG . Cao YX, Wang WW, Ma SF, Yao T, Zhu YC . Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes. Cardiovasc Res 2008; 79: 632–41.
Wang YF, Mainali P, Tang CS, Shi L, Zhang CY, Yan H, et al. Effects of nitric oxide and hydrogen sulfide on the relaxation of pulmonary arteries in rats. Chin Med J 2008; 121: 420–3.
Wang Y, Zhao X, Jin H, Wei H, Li W, Bu D, et al. Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoprotein E knockout mice. Aterioscler Thromb Vasc Biol 2009; 29: 173–9.
Olson KR, Whitfield NL, Bearden SE . St Leger J, Nilson E, Gao Y, et al. Hypoxic pulmonary vasodilation: a paradigm shift with a hydrogen sulfide mechanism. Am J Physiol Regul Integr Comp Physiol 2010; 298: R51–60.
Shaul PW, Magness RR, Muntz KH, DeBeltz D, Buja LM . Alpha 1-adrenergic receptors in pulmonary and systemic vascular smooth muscle. Alterations with development and pregnancy. Circ Res 1990; 67: 1193–200.
Rochette L, Vergely C . Hydrogen sulfide (H2S), an endogenous gas with odor of rotten eggs might be a cardiovascular function regulator. Ann Cardiol Angeiol (Paris) 2008; 57: 136–8.
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.
Seto SW, Ho YY, Hui HN, Au AL, Kwan YW . Contribution of glibenclamide-sensitive, ATP-dependent K+ channel activation to acetophenone analogues-mediated in vitro pulmonary artery relaxation of rat. Life Sci 2006; 78: 631–9.
Fan LH, Tian HY, Wang J, Huo JH, Hu Z, Ma AQ, et al. Downregulation of Kir6.1/SUR2B channels in the obese rat aorta. Nutrition 2009, 25: 359–63.
Yang W, Yang GD, Jia XM, Wu LY, Wang R . Activation of KATP channels by H2S in rat insulin-secreting cells and the underlying mechanisms. J Physiol 2005; 569: 519–31.
Lu T, Ye D, Wang X, Seubert JM, Graves JP, Bradbury JA, et al. Cardiac and vascular KATP channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanisms. J Physiol 2006; 575: 627–44.
Wang T, Zhang ZX, Xu YJ . Effect of mitochondrial KATP channel on voltage- gated K+ channel in 24 hour-hypoxic human pulmonary artery smooth muscle cells. Chin Med J 2005; 118: 12–9.
Cyrino FZ, Bottino DA, Coelho FC, Ravel D, Bouskela E . Effects of sulfonylureas on KATP channel-dependent vasodilation. J Diabetes Complications 2003; 17: 6–10.
Peter P, Ashcroft FM . Modeling KATP channel gating and its regulation. Prog Biophys Mol Biol 2009; 99: 7–19.
Fujita A, Kurachi Y . Molecular aspects of ATP-sensitive K+ channels in the cardiovascular system and K+ channel openers. Pharmacol Ther 2000; 85: 39–53.
Kane GC, Liu XK, Yamada S, Olson TM, Terzic A . Cardiac KATP channels in health and disease. J Mol Cell Cardiol 2005; 38: 937–43.
Cao K, Tang GH, Hu DH, Wang R . Molecular basis of ATP-sensitive K+ channels in rat vascular smooth muscles. Biochem Biophys Res Commun 2002; 296: 463–9.
Acknowledgements
This work was supported by the Foundation of the Ministry of Education, People's Republic of China (20070001702 and 20070001770); the National Natural Science Foundation of China 81070212, 30821001, and 30801251); the Major Basic Research Development Program of the People's Republic of China (2011CB503904); and the Beijing Natural Science Foundation (7082095).
We thank Shu-xu DU and Wei LU for their technical assistance.
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Sun, Y., Tang, Cs., Jin, Hf. et al. The vasorelaxing effect of hydrogen sulfide on isolated rat aortic rings versus pulmonary artery rings. Acta Pharmacol Sin 32, 456–464 (2011). https://doi.org/10.1038/aps.2011.9
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DOI: https://doi.org/10.1038/aps.2011.9
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