| Autor: |
Potthoff SA; Department of Nephrology, Medical Faculty, Heinrich-Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany. johannes.stegbauer@med.uni-duesseldorf.de., Fähling M, Clasen T, Mende S, Ishak B, Suvorava T, Stamer S, Thieme M, Sivritas SH, Kojda G, Patzak A, Rump LC, Stegbauer J |
| Jazyk: |
angličtina |
| Zdroj: |
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2014 Feb; Vol. 63 (2), pp. 265-72. Date of Electronic Publication: 2013 Nov 04. |
| DOI: |
10.1161/HYPERTENSIONAHA.113.02289 |
| Abstrakt: |
Apolipoprotein E-deficient (apoE(-/-)) mice fed on Western diet are characterized by increased vascular resistance and atherosclerosis. Previously, we have shown that chronic angiotensin (Ang)-(1-7) treatment ameliorates endothelial dysfunction in apoE(-/-) mice. However, the mechanism of Ang-(1-7) on vasoconstrictor response to Ang II is unknown. To examine Ang-(1-7) function, we used apoE(-/-) and wild-type mice fed on Western diet that were treated via osmotic minipumps either with Ang-(1-7) (82 μg/kg per hour) or saline for 6 weeks. We show that Ang II-induced renal pressor response was significantly increased in apoE(-/-) compared with wild-type mice. This apoE(-/-)-specific response is attributed to reactive oxygen species-mediated p38 mitogen-activated protein kinase activation and subsequent phosphorylation of myosin light chain (MLC(20)), causing renal vasoconstriction. Here, we provide evidence that chronic Ang-(1-7) treatment attenuated the renal pressor response to Ang II in apoE(-/-) mice to wild-type levels. Ang-(1-7) treatment significantly decreased renal inducible nicotinamide adenine dinucleotide phosphate subunit p47phox levels and, thus, reactive oxygen species production that in turn causes decreased p38 mitogen-activated protein kinase activity. The latter has been confirmed by administration of a specific p38 mitogen-activated protein kinase inhibitor SB203580 (5 μmol/L), causing a reduced renal pressor response to Ang II in apoE(-/-) but not in apoE(-/-) mice treated with Ang-(1-7). Moreover, Ang-(1-7) treatment had no effect in Mas(-/-)/apoE(-/-) double-knockout mice confirming the specificity of Ang-(1-7) action through the Mas-receptor. In summary, Ang-(1-7) modulates vascular function via Mas-receptor activation that attenuates pressor response to Ang II in apoE(-/-) mice by reducing reactive oxygen species-mediated p38 mitogen-activated protein kinase activity. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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