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|Title:||Role of hydrogen sulphide in haemorrhagic shock in the rat: Protective effect of inhibitors of hydrogen sulphide biosynthesis|
Mohammed Atan, M.S.B.
|Citation:||Mok, Y.-Y.P., Mohammed Atan, M.S.B., Ping, C.Y., Jing, W.Z., Bhatia, M., Moochhala, S., Moore, P.K. (2004-12). Role of hydrogen sulphide in haemorrhagic shock in the rat: Protective effect of inhibitors of hydrogen sulphide biosynthesis. British Journal of Pharmacology 143 (7) : 881-889. ScholarBank@NUS Repository. https://doi.org/10.1038/sj.bjp.0706014|
|Abstract:||1 Haemorrhagic shock (60 min) in the anaesthetized rat resulted in a prolonged fall in the mean arterial blood pressure (MAP) and heart rate (HR). 2 Pre-treatment (30 min before shock) or post-treatment (60 min after shock) with inhibitors of cystathionine γ lyase (CSE; converts cysteine into hydrogen sulphide (H 2S)), d1-propargylglycine or β-cyanoalanine (50 mg kg -1, i.V.), or glibenclamide (40 mg kg -1, i.p.), produced a rapid, partial restoration in MAP and HR. Neither saline nor DMSO affected MAP or HR. 3 Plasma H 2S concentration was elevated 60min after blood withdrawal (37.5 ± 1.3 μm, n = 18 c.f. 28.9 ± 1.4 μm, n = 15, P < 0.05). 4 The conversion of cysteine to H 2S by liver (but not kidney) homogenates prepared from animals killed 60 min after withdrawal of blood was significantly increased (52.1 ± 1.6 c.f. 39.8 ± 4.1 nmol mg protein -1, n = 8, P < 0.05) as was liver CSE mRNA (2.7 ×). Both PAG (IC 50, 55.0 ± 3.2 μm) and BCA (IC 50, 6.5 ± 1.2 μm) inhibited liver H 2S synthesizing activity in vitro. 5 Pre-treatment of animals with PAG or BCA (50 mg kg -1, i.p.) but not glibenclamide (40 mg kg -1, i.p., K ATP channel inhibitor) abolished the rise in plasma H 2S in animals exposed to 60 min haemorrhagic shock and prevented the augmented biosynthesis of H 2S from cysteine in liver. 6 These results demonstrate that H 2S plays a role in haemorrhagic shock in the rat. CSE inhibitors may provide a novel approach to the treatment of haemorrhagic shock.|
|Source Title:||British Journal of Pharmacology|
|Appears in Collections:||Staff Publications|
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