Abstract | OBJECTIVES: METHODS: Male adult Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 h post-CLP, a bolus intravenous injection of 2 nmol ghrelin was followed by a continuous infusion of 12 nmol ghrelin via a primed mini-pump over 15 h. At 20 h post-CLP (i.e., severe sepsis), cardiac output (CO), stroke volume (SV), TPR, and organ blood flow were measured using (141)Ce-microspheres. Plasma ET-1 levels and preproET-1 gene expression in the liver, small intestine, and kidneys were measured by ELISA and RT-PCR, respectively. The direct effect of ghrelin on ET-1 production was studied using cultured human umbilical vein endothelial cells (HUVECs) treated with tumor necrosis factor-alpha ( TNF-alpha). RESULTS: CONCLUSIONS: The improvement of tissue perfusion by ghrelin in severe sepsis appears to be mediated by downregulation of ET-1 involving a NF-kappaB-dependent pathway.
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Authors | Rongqian Wu, Weifeng Dong, Mian Zhou, Xiaoxuan Cui, H Hank Simms, Ping Wang |
Journal | Cardiovascular research
(Cardiovasc Res)
Vol. 68
Issue 2
Pg. 318-26
(Nov 01 2005)
ISSN: 0008-6363 [Print] England |
PMID | 16018991
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Endothelin-1
- Ghrelin
- NF-kappa B
- Peptide Hormones
- Tumor Necrosis Factor-alpha
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Topics |
- Acute Disease
- Animals
- Cells, Cultured
- Colonic Diseases
(blood, drug therapy)
- Down-Regulation
- Endothelial Cells
(drug effects, metabolism)
- Endothelin-1
(blood, metabolism)
- Enzyme-Linked Immunosorbent Assay
- Ghrelin
- Infusions, Intravenous
- Intestine, Small
(blood supply)
- Kidney
(blood supply)
- Liver
(blood supply)
- Male
- Microspheres
- NF-kappa B
(metabolism)
- Peptide Hormones
(pharmacology, therapeutic use)
- Perfusion
- Rats
- Rats, Sprague-Dawley
- Regional Blood Flow
- Reverse Transcriptase Polymerase Chain Reaction
- Sepsis
(blood, drug therapy)
- Tumor Necrosis Factor-alpha
(pharmacology)
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