Journal article
Tumor necrosis factor-α impairs contraction but not relaxation in carotid arteries from iNOS-deficient mice
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.279(5), pp.R1558-R1564
11/01/2000
DOI: 10.1152/ajpregu.2000.279.5.R1558
PMID: 11049836
Abstract
We used mice deficient in expression of inducible NO synthase (iNOS −/−) to directly examine the role of iNOS in impaired vasoconstrictor responses following tumor necrosis factor-α (TNF-α). In iNOS +/+ mice, contraction of carotid arteries in response to prostaglandin F2α (PGF2α) was impaired following TNF-α (100 μg/kg ip)( n = 10, P < 0.01). In contrast to responses in wild-type mice, contraction to low concentrations of PGF2α were normal, but maximum contraction to PGF2α was impaired in arteries from iNOS −/− mice treated with TNF-α [0.35 ± .0.02 g ( n = 8) following vehicle and 0.25 ± 0.02 g ( n = 7) following TNF-α ( P < 0.05)]. Aminoguanidine, a relatively selective inhibitor of iNOS, partially restored contraction to PGF2α in vessels from iNOS +/+ mice but had no effect in iNOS −/− mice injected with TNF-α, suggesting that a mechanism(s) other than iNOS contributes to impaired responses. In contrast to contractile responses, relaxation of the carotid artery in response to acetylcholine and nitroprusside was not altered following TNF-α in iNOS +/+ or iNOS −/−mice. Responses of carotid arteries from iNOS −/− mice and effects of aminoguanidine suggest that both iNOS-dependent and iNOS-independent mechanisms contribute to impaired contractile responses following TNF-α.
Details
- Title: Subtitle
- Tumor necrosis factor-α impairs contraction but not relaxation in carotid arteries from iNOS-deficient mice
- Creators
- Carol A Gunnett - Departments of Internal Medicine and Pharmacology, and Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242Donald D Heistad - Departments of Internal Medicine and Pharmacology, and Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242Angela Loihl - Departments of Internal Medicine and Pharmacology, and Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242Frank M Faraci - Departments of Internal Medicine and Pharmacology, and Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.279(5), pp.R1558-R1564
- DOI
- 10.1152/ajpregu.2000.279.5.R1558
- PMID
- 11049836
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Language
- English
- Date published
- 11/01/2000
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040361602771
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