Chronic treatment with angiotensin‐(1‐7) improves renal endothelial dysfunction in apolipoproteinE‐deficient mice

Stegbauer, Johannes; Potthoff, S; Quack, Ivo; Mergia, Evanthia; Clasen, Tilman; Friedrich, Sebastian; Vonend, Oliver; Woznowski, Magdalena; Königshausen, Eva; Sellin, Lorenz; Rump, L. C.

doi:10.1111/j.1476-5381.2011.01295.x

Cited by 46 publications

(42 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 6 weeks, apoE(−/−) mice (groups 2 and 3) were treated with either saline or Ang(1-7) (82 µg/kg per hour) via osmotic mini pumps subcutaneously, as described previously. 24 Another group of apoE(−/−) mice was treated with a p38 MAPK inhib itor (BIRB796, 50 mg/kg per day) from the age of 6 weeks (group 4). In addition, Mas(−/−)/apoE(−/−) doubleknockout mice (groups 5 and 6) were treated as groups 2 and 3.…”

Section: Resultsmentioning

confidence: 99%

“…7,27,30 Previously, we showed that apoE(−/−) fed on a highfat diet exhibit impaired endo thelialdependent vasorelaxation. 24 Chronic Ang(1-7) treat ment improved NO bioavailability and, therefore, ameliorated endothelial dysfunction in these mice.…”

Section: Discussionmentioning

confidence: 99%

“…ApoE(−/−) mice subject to highfat Western diet are characterized by a pronounced vascular dysfunction and rapid progression of atherosclerosis, which is a result of impaired clearance of lowdensity lipoprotein, leading to downregulation of ROS scavenging mechanisms. 9,24,29 In these mice, mechanisms of proper vasorelaxation and vasoconstriction are compromised because of hypercholesterolemia. 7,27,30 Previously, we showed that apoE(−/−) fed on a highfat diet exhibit impaired endo thelialdependent vasorelaxation.…”

Section: Discussionmentioning

confidence: 99%

“…23 Previously, we and others have shown that chronic Ang(1-7) treatment ameliorates endothelial dysfunction in apoE(−/−) mice on a highfat diet. 24,25 However, the effect of Ang(1-7) on vasoconstrictor response to Ang II is yet unknown. Therefore, the aim of the present study was to examine whether chronic Ang(1-7) treatment affects the renal vasoconstrictor response to Ang II in apoE(−/−).…”

Section: February 2014mentioning

confidence: 99%

See 3 more Smart Citations

Angiotensin-(1–7) Modulates Renal Vascular Resistance Through Inhibition of p38 Mitogen-Activated Protein Kinase in Apolipoprotein E–Deficient Mice

et al. 2014

View full text Add to dashboard Cite

Abstract-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 wildtype 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 wildtype 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 wildtype 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 mitogenactivated protein kinase activity. The latter has been confirmed by administration of a specific p38 mitogenactivated 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(−/−) doubleknockout mice confirming the specificity of Ang (1-

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: February 2014mentioning

confidence: 99%

See 2 more Smart Citations

Angiotensin-(1–7) Modulates Renal Vascular Resistance Through Inhibition of p38 Mitogen-Activated Protein Kinase in Apolipoprotein E–Deficient Mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Accordingly, deletion of the receptor Mas resulted in blood pressure increase and endothelial dysfunction (14) whereas Ang-(1-7) infusion improved vascular function by inducing nitric oxide and prostaglandin release (15)(16)(17). Moreover, Ang-(1-7) has been shown to reduce reactive oxygen species production and vascular inflammation, thereby slowing down the progression of atherosclerosis in mice (18). Although many studies have indicated a clear role of the Ang-(1-7)/Mas axis in vascular inflammation, not much is known about the influence of Mas on immune cells and their function during inflammatory processes.…”

mentioning

confidence: 99%

Role of the receptor Mas in macrophage-mediated inflammation in vivo

Hammer

Yang

Friedrich

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Recently, an alternative renin–angiotensin system pathway has been described, which involves binding of angiotensin-(1–7) to its receptor Mas. The Mas axis may counterbalance angiotensin-II–mediated proinflammatory effects, likely by affecting macrophage function. Here we investigate the role of Mas in murine models of autoimmune neuroinflammation and atherosclerosis, which both involve macrophage-driven pathomechanisms. Mas signaling affected macrophage polarization, migration, and macrophage-mediated T-cell activation. Mas deficiency exacerbated the course of experimental autoimmune encephalomyelitis and increased macrophage infiltration as well as proinflammatory gene expression in the spleen and spinal cord. Furthermore, Mas deficiency promoted atherosclerosis by affecting macrophage infiltration and migration and led to increased oxidative stress as well as impaired endothelial function in ApoE-deficient mice. In summary, we identified the Mas axis as an important factor in macrophage function during inflammation of the central nervous and vascular system in vivo. Modulating the Mas axis may constitute an interesting therapeutic target in multiple sclerosis and/or atherosclerosis.

show abstract