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Vascular effects of LPS in mice deficient in expression of the gene for inducible nitric oxide synthase.
- Source :
-
The American journal of physiology [Am J Physiol] 1998 Aug; Vol. 275 (2), pp. H416-21. - Publication Year :
- 1998
-
Abstract
- The inducible isoform of nitric oxide synthase (iNOS) is expressed after systemic administration of lipopolysaccharide (LPS). The importance of expression of iNOS in blood vessels is poorly defined. Because nitric oxide from iNOS may alter vasomotor function, we examined effects of LPS on vasomotor function in carotid arteries from iNOS-deficient mice. We studied contraction of the carotid artery from wild-type and iNOS-deficient mice in vitro 12 h after injection of LPS (20 mg/kg ip). Contractile responses to PGF2alpha (3-30 microM) and thromboxane A2 analog (U-46619; 3-100 nM) were evaluated using vascular rings from mice treated with vehicle or LPS. Maximum force of contraction generated by rings in response to PGF2alpha was 0.39 +/- 0.02 and 0.25 +/- 0.01 (SE) g (n = 14) in vehicle and LPS-treated wild-type mice, respectively (P < 0.001 vs. vehicle). Thus LPS reduced constrictor responses in wild-type mice. Thiocitrulline and aminoguanidine (inhibitors of iNOS) improved contractile responses from LPS-treated wild-type vessels. Indomethacin also improved constrictor responses in arteries from wild-type mice injected with LPS. In contrast, contraction of the carotid arteries in response to PGF2alpha and U-46619 was not impaired in LPS-treated iNOS-deficient mice, and contraction was not altered by inhibitors of iNOS. Expression of iNOS mRNA was confirmed using RT-PCR in carotid arteries from wild-type mice after injection of LPS but not vehicle. PCR products for iNOS were not observed in iNOS-deficient mice. These findings provide the first direct evidence that iNOS mediates impairment of vascular contraction after treatment with LPS.
- Subjects :
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid pharmacology
Animals
Carotid Arteries drug effects
Citrulline analogs & derivatives
Citrulline pharmacology
Dinoprost pharmacology
Enzyme Inhibitors pharmacology
Gene Expression Regulation, Enzymologic drug effects
Guanidines pharmacology
Heterozygote
In Vitro Techniques
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle Contraction drug effects
Muscle, Smooth, Vascular drug effects
Nitric Oxide Synthase deficiency
Nitric Oxide Synthase genetics
Nitric Oxide Synthase Type II
RNA, Messenger biosynthesis
Thiourea analogs & derivatives
Thiourea pharmacology
Transcription, Genetic drug effects
Transcription, Genetic physiology
Vasoconstriction drug effects
Carotid Arteries physiology
Gene Expression Regulation, Enzymologic physiology
Lipopolysaccharides pharmacology
Muscle, Smooth, Vascular physiology
Nitric Oxide Synthase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9513
- Volume :
- 275
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The American journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 9683428
- Full Text :
- https://doi.org/10.1152/ajpheart.1998.275.2.H416