Document Detail

Resistance to endotoxin shock in spontaneously hypertensive rats.
MedLine Citation:
PMID:  9622153     Owner:  NLM     Status:  MEDLINE    
Septic shock involves systemic vasodilation mediated by proinflammatory cytokines. In essential hypertension, vascular and immune dysfunctions are closely associated. The response of hypertensive animals compared with normotensive controls to endotoxin (lipopolysaccharide; LPS) challenge is not known. Age-matched (12 weeks) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to intravenous injection of 10 mg/kg LPS. Survival rate at 24 hours was markedly higher in SHR than in WKY (12 of 15 and 3 of 15, respectively; P<0.01). Survival of LPS-injected SHR was not related to their hypertension because hydralazine-treated SHR with normalized pressure had similar survival rates, and WKY made hypertensive by clipping of one renal artery showed fatality similar to that of normotensive WKY. Continuous arterial pressure and sequential plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured in LPS-treated SHR and WKY. Both the duration of the delayed hypotensive phase and the systemic release of IL-6 were much lower in SHR than WKY, whereas both acute hypotension and plasma TNF peak were equivalent. We further explored in vitro the inflammatory response and showed that LPS-activated whole blood from SHR produced less TNF and IL-6 than WKY LPS-activated whole blood. Our results indicate that SHR have a greater ability to resist endotoxic shock than WKY. This is not related to their hypertension but is associated with an attenuated inflammatory response to LPS.
C Bernard; R Merval; B Esposito; A Tedgui
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  31     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-06-19     Completed Date:  1998-06-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1350-6     Citation Subset:  IM    
INSERM U141 and IFR Circulation-Lariboisière, Hôpital Lariboisière, Paris, France.
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MeSH Terms
Antihypertensive Agents / pharmacology
Hydralazine / pharmacology
Immunity, Innate
Injections, Intravenous
Interleukin-6 / blood
Lipopolysaccharides / administration & dosage
Rats, Inbred SHR / physiology*
Rats, Inbred WKY
Shock, Septic / blood,  immunology*,  mortality
Time Factors
Tumor Necrosis Factor-alpha / analysis
Reg. No./Substance:
0/Antihypertensive Agents; 0/Interleukin-6; 0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 86-54-4/Hydralazine

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