Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis.

Abstract

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 gamma lyase (CSE; converts cysteine into hydrogen sulphide (H(2)S)), dl-propargylglycine or beta-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 microM, n=18 c.f. 28.9+/-1.4 microM, 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 x). Both PAG (IC(50), 55.0+/-3.2 microM) and BCA (IC(50), 6.5+/-1.2 microM) 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.

• Authors: Ying-Yuan Pamela Mok, Mohammed Shirhan Bin Mohammed Atan, Cheong Yoke Ping, Wang Zhong Jing, Madhav Bhatia, Shabbir Moochhala, Philip K Moore
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 143 Issue 7 Pg. 881-9 (Dec 2004) ISSN: 0007-1188 [Print] England
• PMID: 15504752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-Binding Cassette Transporters
• Alkynes
• Enzyme Inhibitors
• Hypoglycemic Agents
• KATP Channels
• Potassium Channels
• Potassium Channels, Inwardly Rectifying
• RNA, Messenger
• uK-ATP-1 potassium channel
• propargylglycine
• 3-cyanoalanine
• Cystathionine gamma-Lyase
• Cysteine
• Alanine
• Glyburide
• Glycine
• Hydrogen Sulfide

Topics

• ATP-Binding Cassette Transporters
• Alanine (analogs & derivatives, pharmacology)
• Alkynes (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Cystathionine gamma-Lyase (antagonists & inhibitors, biosynthesis)
• Cysteine (metabolism)
• Enzyme Inhibitors (pharmacology)
• Glyburide (pharmacology)
• Glycine (analogs & derivatives, pharmacology)
• Heart Rate (drug effects)
• Hydrogen Sulfide (antagonists & inhibitors, blood, metabolism)
• Hypoglycemic Agents (pharmacology)
• KATP Channels
• Liver (drug effects, enzymology, metabolism)
• Male
• Potassium Channels (metabolism)
• Potassium Channels, Inwardly Rectifying
• RNA, Messenger (biosynthesis, genetics)
• Rats
• Rats, Sprague-Dawley
• Shock, Hemorrhagic (physiopathology, prevention & control)