Activation of the Mas receptors by AVE0991 and MrgD receptor using Alamandine to limit the deleterious effects of Ang II‐induced hypertension

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Tanriverdi L. H., Özhan O., Ulu A., Yildiz A., Ateş B., Vardi N., ...Daha Fazla

FUNDAMENTAL AND CLINICAL PHARMACOLOGY, cilt.1, sa. 1, ss.1-15, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1 Sayı: 1
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1111/fcp.12829
  • Dergi Adı: FUNDAMENTAL AND CLINICAL PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1-15
  • Anahtar Kelimeler: alamandine, angiotensin II, AVE0991, cyclophilin A, hypertension, NADPH oxidase
  • İnönü Üniversitesi Adresli: Evet

Özet

Objectives

The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin-angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II-induced hypertension in rats.

Materials-Methods

Sprague Dawley rats were subject to 4-week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 μg/kg), AVE0991 (576 μg/kg), or ALA+AVE0991 during the last two weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail-cuff plethysmography at 1, 15, and 29 days post-treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses.

Results

SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin-A (CYP-A), monocyte chemoattractant protein-1 (MCP-1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase-2 and -9, NADPH oxidase-4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP-1 and CYP-A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin-converting enzyme-2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group.

Conclusions

Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II-induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.