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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zemse, Saiprasad M. Hilgers, Rob H. P. Simkins, G. Bryan Rudic, R. Daniel Webb, R. Clinton |
| Description | Country affiliation: United States Author Affiliation: Zemse SM ( Department of Physiology, Medical College of Georgia, Augusta, GA 30912-3000, USA. szemse@students.mcg.edu) |
| Abstract | Endothelin-1 (ET-1) is implicated in the development of endothelial dysfunction through the generation of reactive oxygen species by NADPH oxidase activation. Interleukin-10 (IL-10) is an antiinflammatory cytokine that stimulates nitric oxide production, decreases superoxide production, and restores endothelial integrity after vascular injury. In this study, we tested whether IL-10 attenuates ET-1-induced endothelial dysfunction by improving acetylcholine (ACh)-induced relaxation of cultured murine aortic rings. Aortic rings (2 mm long) of C57BL/6 mice were incubated in 2 mL DMEM containing 120 U/mL penicillin and 120 microg/mL streptomycin in the presence of one of 4 treatments: vehicle (deionized water), ET-1 (100 nmol/L), recombinant mouse IL-10 (300 ng/mL), or a combination of both ET-1 and IL-10. After incubation at 37 degrees C for either 1 or 6 h (short-term exposure) or 22 h (overnight exposure), rings were mounted in a wire myograph and stretched to a passive force of 5 mN. Endothelium-dependent vasorelaxation was assessed by constructing cumulative concentration-response curves to ACh (0.001-10 micromol/L) during 10 mumol/L phenylephrine (PE)-induced contraction. Short-term exposure of ET-1 did not result in an impairment of ACh-induced relaxation. Overnight exposure of aortic rings to ET-1 resulted in a statistically significant endothelial dysfunction characterized by a reduced maximal relaxation response to ACh compared with that of untreated rings (Emax 57% +/- 3% versus 82% +/- 4%). IL-10 treatment restored ACh-induced relaxation (Emax 77% +/- 3%). Western blotting showed decreased eNOS expression in response to ET-1, whereas vessels treated with a combination of ET-1 and IL-10 showed increased expression of eNOS. Immunohistochemical analysis showed decreased eNOS expression in ET-1-treated vessels compared with those treated with both ET-1 and IL-10. We conclude that, in murine aorta, the antiinflammatory cytokine IL-10 prevents impairment in endothelium-dependent relaxation induced in response to long-term incubation with ET-1 via normalization of eNOS expression. |
| File Format | HTM / HTML |
| ISSN | 00084212 |
| e-ISSN | 12057541 |
| DOI | 10.1139/Y08-049 |
| Journal | Canadian Journal of Physiology and Pharmacology |
| Issue Number | 8 |
| Volume Number | 86 |
| Language | English |
| Publisher | Canadian Science Publishing |
| Publisher Date | 2008-08-01 |
| Publisher Place | Canada |
| Access Restriction | Open |
| Subject Keyword | Discipline Physiology Discipline Pharmacology Endothelin-1 Pharmacology Endothelium, Vascular Physiology Interleukin-10 Muscle Relaxation Drug Effects Muscle, Smooth, Vascular Acetylcholine Animals Aorta, Thoracic Blotting, Western Down-regulation Fluorescent Antibody Technique Immunohistochemistry In Vitro Techniques Mice Mice, Inbred C57bl Nitric Oxide Donors Nitric Oxide Synthase Type Iii Antagonists & Inhibitors Biosynthesis Nitroprusside Phenylephrine Vasoconstrictor Agents Vasodilator Agents |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Pharmacology |
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