Mas Receptor Activation Contributes to the Improvement of Nitric Oxide Bioavailability and Vascular Remodeling During Chronic AT1R (Angiotensin Type-1 Receptor) Blockade in Experimental Hypertension

Autor: Carmine Nicoletti, Emanuele Arrabito, Rhian M. Touyz, Antonio Filippini, Massimo Volpe, Carmine Savoia, Allegra Battistoni, Luca Madaro, Rosa Parente, Ulrike Muscha Steckelings
Rok vydání: 2020
Předmět:
0301 basic medicine
Angiotensin receptor
Tetrazoles
Blood Pressure
030204 cardiovascular system & hematology
Proto-Oncogene Mas
Receptors
G-Protein-Coupled

chemistry.chemical_compound
0302 clinical medicine
Enos
Rats
Inbred SHR

angiotensins
oxidative stress
Receptor
Mesenteric arteries
Mice
Knockout

biology
Chemistry
Angiotensin II
resistance arteries
Imidazoles
Mesenteric Arteries
Vasodilation
medicine.anatomical_structure
Hypertension
Olmesartan
medicine.drug
medicine.medical_specialty
Nitric Oxide Synthase Type III
vascular remodeling
Vascular Remodeling
Nitric Oxide
Receptor
Angiotensin
Type 2

Receptor
Angiotensin
Type 1

Nitric oxide
03 medical and health sciences
nitric oxide
Proto-Oncogene Proteins
Internal medicine
Renin–angiotensin system
Internal Medicine
medicine
Animals
angiotensin receptor blockers
angiotensin receptors
biology.organism_classification
Peptide Fragments
030104 developmental biology
Endocrinology
Angiotensin II Type 1 Receptor Blockers
Zdroj: Savoia, C, Arrabito, E, Parente, R, Nicoletti, C, Madaro, L, Battistoni, A, Filippini, A, Steckelings, U M, Touyz, R M & Volpe, M 2020, ' Mas Receptor Activation Contributes to the Improvement of Nitric Oxide Bioavailability and Vascular Remodeling During Chronic AT1R (Angiotensin Type-1 Receptor) Blockade in Experimental Hypertension ', Hypertension, vol. 76, no. 6, pp. 1753-1761 . https://doi.org/10.1161/HYPERTENSIONAHA.120.15527
ISSN: 1524-4563
0194-911X
DOI: 10.1161/hypertensionaha.120.15527
Popis: Angiotensin (1–7) production increases during AT1R (angiotensin type-1 receptor) blockade. The contribution of Ang (1–7) (angiotensin [1–7]) and its receptor (MasR) to the favorable effect of angiotensin receptor blockers on remodeling and function of resistance arteries remains unclear. We sought to determine whether MasR contributes to the improvement of vascular structure and function during chronic AT1R blockade. Spontaneously hypertensive rats were treated with Ang (1–7) or olmesartan ± MasR antagonist A-779, or vehicle, for 14 days. Blood pressure was measured by tail cuff methodology. Mesenteric arteries were dissected and mounted on a pressurized micromyograph to evaluate media-to-lumen ratio (M/L) and endothelial function. Expression of MasR and eNOS (endothelial nitric oxide synthase) was evaluated by immunoblotting, plasma nitrate by colorimetric assay, and reactive oxygen species production by dihydroethidium staining. Independently of blood pressure, olmesartan significantly reduced M/L and improved NO bioavailability, A-779 prevented these effects. Likewise, Ang (1–7) significantly reduced M/L and NO bioavailability. MasR expression was significantly increased by Ang (1–7) as well as by olmesartan, and it was blunted in the presence of A-779. Both Ang (1–7) and olmesartan increased eNOS expression and plasma nitrite which were reduced by A-779. Superoxide generation was attenuated by olmesartan and Ang (1–7) and was blunted in the presence of A-779. These MasR-mediated actions were independent of AT2R activation since olmesartan and Ang (1–7) increased MasR expression and reduced M/L in Ang II (angiotensin II)–infused AT2R knockout mice, independently of blood pressure control. A-779 prevented these effects. Hence, MasR activation may contribute to the favorable effects of AT1R antagonism on NO bioavailability and microvascular remodeling, independently of AT2R activation and blood pressure control.
Databáze: OpenAIRE