Journal article
Vascular Effects of Lipopolysaccharide Are Enhanced in Interleukin-10–Deficient Mice
Stroke (1970), Vol.30(10), pp.2191-2196
10/1999
DOI: 10.1161/01.STR.30.10.2191
PMID: 10512928
Abstract
Background and purpose: The role in blood vessels of interleukin-10 (IL-10), a potent anti-inflammatory cytokine, is not known. Using mice with targeted deletion of the gene for IL-10 (IL-10(-/-)), we examined the hypothesis that IL-10 is a major modulator of the vascular effects of lipopolysaccharide (LPS). Methods-We examined in vitro responses of carotid arteries obtained from wild-type (129/SvEv or C57BL/6; IL-10(+/+)) and IL-10-deficient mice 6 hours after injection of a relatively low dose of LPS (10 microgram).
Results: Contraction of the carotid artery in response to U46619 was impaired in IL-10-deficient mice treated with LPS compared with LPS-treated controls. After LPS, U46619 (0.03 and 0.1 microgram/mL) contracted the carotid artery by 0.11+/-0.02 (mean+/-SEM) and 0.38+/-0.03 g in wild-type (n=10) and 0.03+/-0.01 and 0.19+/-0.03 g in IL-10-deficient (n=8) mice (P<0.05 versus control). Aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), had no significant effect on contraction of the carotid artery from LPS-treated control mice but restored contraction of the carotid artery in response to U46619 in IL-10-deficient mice to levels seen in wild-type mice. Similar findings were obtained when phenylephrine was used as a vasoconstricting agent. These findings indicate that LPS produces much greater impairment of contractile responses of the carotid artery in IL-10-deficient mice than in control mice. Impaired contractile function was eliminated by aminoguanidine, suggesting that expression of iNOS is enhanced in arteries from IL-10-deficient mice. In carotid arteries from animals injected with LPS, reverse transcription-polymerase chain reaction (RT-PCR) products for iNOS were found more frequently in IL-10-deficient mice than in wild-type mice. RT-PCR products for iNOS were not present in arteries from vehicle-treated animals (IL-10-deficient or wild-type mice).
Conclusions: This is the first evidence that endogenous IL-10 is a major determinant of the effects of LPS on vascular tone. The results suggest that impaired constrictor responses of the carotid artery after LPS in IL-10-deficient mice are mediated by enhanced expression of iNOS.
Details
- Title: Subtitle
- Vascular Effects of Lipopolysaccharide Are Enhanced in Interleukin-10–Deficient Mice
- Creators
- Carol A Gunnett - From the Departments of Internal Medicine (C.A.G., D.J.B., F.M.F.) and Pharmacology (F.M.F), Cardiovascular Center, University of Iowa College of Medicine, Iowa CityDaniel J Berg - From the Departments of Internal Medicine (C.A.G., D.J.B., F.M.F.) and Pharmacology (F.M.F), Cardiovascular Center, University of Iowa College of Medicine, Iowa CityFrank M Faraci - From the Departments of Internal Medicine (C.A.G., D.J.B., F.M.F.) and Pharmacology (F.M.F), Cardiovascular Center, University of Iowa College of Medicine, Iowa City
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.30(10), pp.2191-2196
- DOI
- 10.1161/01.STR.30.10.2191
- PMID
- 10512928
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 10/1999
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040305202771
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