Favorable Vascular Actions of Angiotensin-(1–7) in Human Obesity
Abstract
Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1–mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1–7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1–7) on vasodilator tone and endothelin-1–dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1–7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1–7) administration compared with saline (both P >0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1–7) ( P =0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified ( P =0.91). Finally, Ang-(1–7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P <0.001); nitric oxide inhibition by l - N -monomethylarginine (4 µmol/min) during concurrent endothelin A antagonism resulted in similar vasoconstriction in the absence or presence of Ang-(1–7 Ang-(1–7) ( P =0.69). Our findings indicate that in obese patients Ang-(1–7) has favorable effects not only to improve insulin-stimulated endothelium-dependent vasodilation but also to blunt endothelin-1–dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1–7) to counteract the hemodynamic abnormalities of human obesity.
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In obese humans, angiotensin 1-7 administration decreased vascular dysfunction related to impaired insulin sensitivity.
“In obese humans, Ang-(1-7) administration decreased vascular dysfunction related to impaired insulin sensitivity [140].”
From The critical role of oxidative stress in sarcopenic obesity (2021) · cites this paper as [140]
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- Authors
- Schinzari, F., Tesauro, M., Veneziani, A., Mores, N., Di Daniele, N., & Cardillo, C.
- Affiliations
- University of Rome Tor Vergata (IT)
- From the Policlinico A. Gemelli, Rome, Italy (F.S., A.V., N.M., C.C.); Department of Internal Medicine, University of Tor Vergata, Rome, Italy (M.T., N.D.D.); and Departments of Surgery (A.V.), Pharmacology (N.M.), and Internal Medicine (C.C.), Catholic University, Rome, Italy.
- Venue
- Hypertension
- Published
- 2018-01
- Volume
- 71
- Issue
- 1
- Pages
- 185-191
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2774046602
- Cited by
- 57
- References
- 51
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 11 · 2020: 10 · 2019: 7 · 2018: 3 · 2017: 1
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Funders
- Ministero della Salute (RF 2010, RF-2010-2313809)
- Università Cattolica del Sacro Cuore
- Fondazione Roma (NCDS-2013-00000308)
- 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), obesity, vascular dysfunction, endothelin-1, ETA receptor, endothelium-dependent vasodilation, Mas receptor, forearm blood flow, nitric oxide, A779, BQ-123, L-NMMA, angiotensin II
- MeSH terms
- Adult, Angiotensin I, Female, Forearm, Humans, Insulin, Male, Middle Aged, Obesity, Peptide Fragments, Regional Blood Flow, Statistics as Topic, Vasoconstriction, Vasoconstrictor Agents, Vasodilation, Vasodilator Agents, Endothelin-1, Receptor, Endothelin A
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