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Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis
Author(s) -
Mok YingYuan Pamela,
Mohammed Atan Mohammed Shirhan Bin,
Ping Cheong Yoke,
Jing Wang Zhong,
Bhatia Madhav,
Moochhala Shabbir,
Moore Philip K
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706014
Subject(s) - glibenclamide , chemistry , cysteine , shock (circulatory) , saline , in vitro , cystathionine beta synthase , endocrinology , pharmacology , medicine , kidney , cystathionine gamma lyase , biochemistry , enzyme , diabetes mellitus
Haemorrhagic shock (60 min) in the anaesthetized rat resulted in a prolonged fall in the mean arterial blood pressure (MAP) and heart rate (HR). 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 2 S)), dl‐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. Plasma H 2 S concentration was elevated 60 min after blood withdrawal (37.5±1.3 μ m, n =18 c.f. 28.9±1.4 μ m, n =15, P <0.05). The conversion of cysteine to H 2 S 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 μ m) and BCA (IC 50 , 6.5±1.2 μ m) inhibited liver H 2 S synthesizing activity in vitro . 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 2 S in animals exposed to 60 min haemorrhagic shock and prevented the augmented biosynthesis of H 2 S from cysteine in liver. These results demonstrate that H 2 S plays a role in haemorrhagic shock in the rat. CSE inhibitors may provide a novel approach to the treatment of haemorrhagic shock.British Journal of Pharmacology (2004) 143 , 881–889. doi: 10.1038/sj.bjp.0706014