Prolonged treatment with angiotensin 1–7 improves endothelial function in diet-induced obesity
Open accessAbstract
OBJECTIVE: The renin-angiotensin system peptides are critically involved in the regulation of endothelial function with important pathological implications. Angiotensin (Ang) 1-7 has many beneficial effects in the vasculature that modulate the cardiovascular risk. Here, we tested the hypothesis that Ang 1-7 has a protective role against the endothelial defects associated with diet-induced obesity (DIO) in mice. METHODS: Ang 1-7 (with or without Ang II) was delivered subcutaneously for 4 weeks using osmotic minipumps. Vascular studies were performed using aortic rings. Arterial pressure and heart rate were measured in separate cohorts of mice by telemetry. RESULTS: First, we examined whether chronic administration of Ang 1-7 improves the vascular dysfunctions caused by Ang II. Subcutaneous coinfusion of Ang 1-7 significantly attenuates Ang II-induced endothelial dysfunctions. In addition, DIO mice have significant impairment in the endothelium-dependent relaxation. The contractile responses induced by various stimuli, including serotonin and endothelin-1, were differentially altered in DIO mice. Notably, DIO mice treated with Ang 1-7 for 4 weeks displayed significant improvement in the endothelial function as indicated by the increased acetylcholine-induced relaxation. Consistent with this, chronic treatment with Ang 1-7 reversed the increased aortic expression of NAD(P)H oxidase subunits (p22(phox) and p47(phox)) and plasma TBARS associated with DIO mice. In contrast, treatment with Ang 1-7 did not normalize the altered contractions associated with DIO mice. CONCLUSION: Our data demonstrate a novel role for Ang 1-7 in improving obesity-associated endothelial dysfunction.
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The efficacy of chronic angiotensin 1-7 treatment in alleviating obesity-associated endothelial vasodilation impairment supports the pathophysiological role of the renin-angiotensin system in obesity-related endothelial dysfunction.
“The efficacy of chronic treatment with Ang 1–7, a peptide that negatively modulate RAS activity, in alleviating obesity-associated impairment in endothelium-dependent vasodilation supports further the pathophysiological role of the RAS in obesity-related endothelial dysfunction (73).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [73]
Chronic treatment with angiotensin 1-7 alleviates obesity-associated impairment in endothelium-dependent vasodilation.
“The efficacy of chronic treatment with Ang 1–7, a peptide that negatively modulate RAS activity, in alleviating obesity-associated impairment in endothelium-dependent vasodilation supports further the pathophysiological role of the RAS in obesity-related endothelial dysfunction (73).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [73]
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The ACE2/angiotensin-(1-7)/MAS Axis of the renin-angiotensin system: focus on angiotensin-(1-7)
Santos, R. A. S., Sampaio, W. O., Alzamora, A. C., Motta-Santos, D., Alenina, N., Bader, M., & Campagnole-Santos, M. J. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2016 · Cited by 1,144 · see citing works
Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis
Rahmouni, K. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.00920 · Cited by 150 · see citing works
Self-citationFavorable Vascular Actions of Angiotensin-(1–7) in Human Obesity
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- Authors
- Beyer, A. M., Guo, D.-F., & Rahmouni, K.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Rahmouni, Kamal
- Venue
- Journal of Hypertension
- Published
- 2013-04
- Volume
- 31
- Issue
- 4
- Pages
- 730-738
- ISSN
- 0263-6352 (ISSN-L)
- PMC
- PMC5684878
- OpenAlex
- W2314297026
- Cited by
- 37
- References
- 46
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 1 · 2015: 5 · 2014: 6 · 2013: 2
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- Pfizer Pharmaceuticals
- National Heart, Lung, and Blood Institute (HL-014388, HL-07121, P01HL014388, HL-084207, P01HL084207, R01HL113612, T32HL007121)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- angiotensin-(1-7), endothelial dysfunction, diet-induced obesity, angiotensin II, renin-angiotensin system, endothelium-dependent relaxation, NADPH oxidase, oxidative stress, acetylcholine-induced relaxation, endothelin-1, serotonin, arterial pressure, cardiovascular risk
- MeSH terms
- Angiotensin I, Animals, Base Sequence, Diet, Endothelium, Vascular, Male, Mice, Inbred C57BL, Obesity, Peptide Fragments, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Mice
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