Document Detail


Hydrogen sulphide in the hypothalamus causes an ATP-sensitive K+ channel-dependent decrease in blood pressure in freely moving rats.
MedLine Citation:
PMID:  18201837     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hydrogen sulfide (H2S) is a naturally occurring gas that may act as an endogenous signaling molecule. In the brain, H2S is mainly produced by cystathionine beta-synthase (CBS) and its cellular effects have been attributed to interactions with N-methyl-D-aspartate (NMDA) receptors and cyclic adenosine 3',5'-monophosphate (cAMP). In contrast, direct vasodilator actions of H2S are most probably mediated by opening smooth muscle ATP-sensitive K+ (K(ATP)) channels. In the hypothalamus, K(ATP) channel-dependent mechanisms are involved in CNS-mediated regulation of blood pressure. In this report, we investigated the hypothesis that H2S may act via K(ATP) channels in the hypothalamus to regulate blood pressure. Mean arterial blood pressure (MAP) and heart rate were monitored in freely moving rats via a pressure transducer placed in the femoral artery. Drugs were infused via a cannula placed in the posterior hypothalamus. Infusion of 200 microM sodium hydrogen sulfide (NaHS), an H2S donor, into the hypothalamus of freely moving rats reduced MAP and heart rate. Infusion of 300 nM to 3 microM gliclazide dose-dependently blocked the effect of 200 microM NaHS. Infusion of the CBS activator, s-adenosyl-L-methionine (0.1 mM and 1 mM), likewise decreased MAP. Infusion of the CBS inhibitors aminooxyacetic acid (10 mM) and hydroxylamine (20 mM) increased MAP but did not block the effects of infusion of 200 microM NaHS. These data indicate that actions of H2S in the hypothalamus decrease blood pressure and heart rate in freely moving rats. This effect appears to be mediated by a K(ATP) channel-dependent mechanism and mimicked by endogenous H2S.
Authors:
G S Dawe; S P Han; J S Bian; P K Moore
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience     Volume:  152     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-06-30     Completed Date:  2008-08-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  169-77     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Sciences, 28 Medical Drive, Singapore 117456. gavindawe@nus.edu.sg
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism*
Animals
Blood Pressure / drug effects,  physiology*
Cystathionine beta-Synthase / drug effects,  metabolism
Enzyme Inhibitors / pharmacology
Heart Rate / drug effects,  physiology
Hydrogen Sulfide / metabolism*
Hypothalamus / drug effects,  metabolism*
Male
Movement
Potassium Channels / drug effects,  metabolism*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Potassium Channels; 56-65-5/Adenosine Triphosphate; 7783-06-4/Hydrogen Sulfide; EC 4.2.1.22/Cystathionine beta-Synthase

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