Naslov
Angiotensin II-Type 1 Receptor Blockade with Losartan Affects the Expression of Enzymes Involved in Vascular Reactivity and Balance of Vascular Oxidative Stress of Sprague-Dawley Rats

Autori
Mihaljević, Zrinka ; Matić, Anita ; Stupin, Ana ; Jukić, Ivana ; Šušnjara, Petar ; Kozina, Nataša ; Kolobarić, Nikolina ; Mihalj, Martina ; Drenjančević, Ines

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Journal of Vascular Research 56:1–134 / - , 2019, 82-83

Skup
3rd Joint Meeting of the European Society for Microcirculation and the European Vascular Biology Organization (ESM-EVBO 2019)

Mjesto i datum
Maastricht, Nizozemska, 15.04.2019. - 18.04.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
angiotensin II type 1 receptors ; losartan ; vascular reactivity ; oxidative stress ; Sprague-Dawley rats

Sažetak
Introduction: It is well known that RAS (Renin- angiotensin system) mediates its signal transduction and functions via ANGII and ANGII receptors interaction and suppression of ANG II levels with high salt diet leads to increased vascular oxidative stress. Our recent study in healthy rats showed that losartan (angiotensin II type 1 (AT-1R) receptor antagonist) impaired vasodilator response of middle cerebral arteries, increased vascular and systemic oxidative stress, decreased activity of antioxidative enzymes and increased antioxidative enzymes gene expression in vessels. Present study evaluated the effects of losartan on protein expression of AT1 and AT2 (angiotensin II type 1 and 2) receptors, enzymes involved in the mechanisms of vascular reactivity (iNOS, COX-1, COX-2), antioxidative enzymes (SOD-1, SOD-2, SOD-3, GPx4, CAT) and NOX1. Methods: Healthy male Sprague-Dawley 9–11 weeks old rats (n = 36) were divided to a control (LS, n = 18) and LS+Losartan group (n = 18), both fed with standard rat chow with 0, 4% NaCl. Rats from LS+Losartan group received 40 mg of Losartan (daily dose) in drinking water for 7 days. Following dietary protocol, rats were anesthetized with ketamine (75 mg/kg) and midazolam (2.5 mg/kg) and sacrificed by decapitation. Protein expressions were determined by Western blot in surface cerebral vessels. Due to small amount of tissue, brain blood vessels from two animals were pooled for one sample. Images were processed and analyzed with ImageJ software, data were analyzed by t- test and presented as mean±SD. All experimental procedures are conformed to the European Guidelines for the Care and Use of Laboratory Animals (directive 86/609) and were approved by the local and national Ethical Committee (No.525-10/0255-15- 6). Results: Protein expression of GPx4, AT1 and iNOS was significantly decreased in LS+losartan group (GPx4 0.48 ± 0.34, AT1 0.58 ± 0.13, iNOS 0.84 ± 0.20) vs. LS group (GPx4 1.03 ± 0.46, AT1 1.44 ± 0.43, iNOS 1.18 ± 0.23). Expression of COX-2 and NOX1 was significantly increased in LS+losartan group (COX-2 2.99 ± 0.79, NOX1 1.14 ± 0.19) compared to LS (COX-2 1.92 ± 0.96, NOX1 0.92 ± 0.17). Conclusions: This data confirmed our previous observations of increased oxidative stress (possible due the increased NOX1 expression and activity) and impaired vascular reactivity (decreased iNOS expression). Acknowledgement: Supported by Croatian Science Foundation under the project #IP-2014-09-6380: “Impaired Vasorelaxation and Endothelial Leukocyte Interaction (ELI) in Development of Atherosclerotic Lesions – V-ELI Athero”.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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