Chronic treatment with angiotensin‐(1‐7) improves renal endothelial dysfunction in apolipoproteinE‐deficient mice
Open Access
- 3 March 2011
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 163 (5), 974-983
- https://doi.org/10.1111/j.1476-5381.2011.01295.x
Abstract
BACKGROUND AND PURPOSE ApolipoproteinE-deficient [apoE (−/−)] mice, a model of human atherosclerosis, develop endothelial dysfunction caused by decreased levels of nitric oxide (NO). The endogenous peptide, angiotensin-(1-7) [Ang-(1-7)], acting through its specific GPCR, the Mas receptor, has endothelium-dependent vasodilator properties. Here we have investigated if chronic treatment with Ang-(1-7) improved endothelial dysfunction in apoE (−/−) mice. EXPERIMENTAL APPROACH ApoE (−/−) mice fed on a lipid-rich Western diet were divided into three groups and treated via osmotic minipumps with either saline, Ang-(1-7) (82 µg·kg−1·h−1) or the same dose of Ang-(1-7) together with D-Ala-Ang-(1-7) (125 µg·kg−1·h−1) for 6 weeks. Renal vascular function was assessed in isolated perfused kidneys. KEY RESULTS Ang-(1-7)-treated apoE (−/−) mice showed improved renal endothelium-dependent vasorelaxation induced by carbachol and increased renal basal cGMP production, compared with untreated apoE (−/−) mice. Tempol, a reactive oxygen species (ROS) scavenger, improved endothelium-dependent vasorelaxation in kidneys of saline-treated apoE (−/−) mice whereas no effect was observed in Ang-(1-7)-treated mice. Chronic treatment with D-Ala-Ang-(1-7), a specific Mas receptor antagonist, abolished the beneficial effects of Ang-(1-7) on endothelium-dependent vasorelaxation. Renal endothelium-independent vasorelaxation showed no differences between treated and untreated mice. ROS production and expression levels of the NAD(P)H oxidase subunits gp91phox and p47phox were reduced in isolated preglomerular arterioles of Ang-(1-7)-treated mice, compared with untreated mice, whereas eNOS expression was increased. CONCLUSION AND IMPLICATIONS Chronic infusion of Ang-(1-7) improved renal endothelial function via Mas receptors, in an experimental model of human cardiovascular disease, by increasing levels of endogenous NO.Keywords
This publication has 42 references indexed in Scilit:
- Guide to Receptors and Channels (GRAC), 5th editionBritish Journal of Pharmacology, 2011
- Angiotensin-(1-7) Prevents Cardiomyocyte Pathological Remodeling Through a Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate–Dependent PathwayHypertension, 2010
- Guide to Receptors and Channels (GRAC), 4th editionBritish Journal of Pharmacology, 2009
- Transgenic Angiotensin-Converting Enzyme 2 Overexpression in Vessels of SHRSP Rats Reduces Blood Pressure and Improves Endothelial FunctionHypertension, 2008
- Angiotensin-(1-7) Counterregulates Angiotensin II Signaling in Human Endothelial CellsHypertension, 2007
- Differential effects of AT1 receptor and Ca2+ channel blockade on atherosclerosis, inflammatory gene expression, and production of reactive oxygen speciesAtherosclerosis, 2007
- Angiotensin-(1-7) Through Receptor Mas Mediates Endothelial Nitric Oxide Synthase Activation via Akt-Dependent PathwaysHypertension, 2007
- Evaluation of Vascular Function in Apolipoprotein E Knockout Mice With Angiotensin-Dependent Renovascular HypertensionHypertension, 2005
- Short-Term Angiotensin(1-7) Receptor Mas Stimulation Improves Endothelial Function in Normotensive RatsHypertension, 2005
- Evidence for a Functional Interaction of the Angiotensin-(1–7) Receptor Mas With AT 1 and AT 2 Receptors in the Mouse HeartHypertension, 2005