Angiotensin II type 2 receptor blocker PD123319 has more beneficial effects than losartan on ischemia–reperfusion injury and oxidative damage in isolated rat heart

2019 ◽  
Vol 97 (12) ◽  
pp. 1124-1131 ◽  
Author(s):  
Aysu Kilic ◽  
Savas Ustunova ◽  
Cansu Usta ◽  
Huri Bulut ◽  
Ismail Meral ◽  
...  

Our study aimed to determine the effects of losartan and PD123319 in ischemia–reperfusion (IR) injury in isolated perfused rat heart. The study used 40 male Wistar albino rats that were grouped as Control, IR, and IR treatment groups that received losartan (20 mg/kg), PD123319 (20 mg/kg), and losartan+PD123319. The hearts were attached to Langendorff isolated heart system by employing in situ cannulation method, and cardiodynamic parameters were recorded during the experiment. At the end of experiment, hearts were retained for biochemical analysis and all data were statistically evaluated. A partial recovery of cardiodynamic parameters was observed in all treatment groups. A significant increase in oxidative stress parameters were seen in the IR group, whereas all treatment groups exhibited lower increase. Furthermore, levels of all antioxidant parameters were significantly lower in the IR group, but higher in the treatment groups. Effects on all parameters were much more remarkable in the PD123319 group. Levels of angiotensin II and renin were increased (P < 0.001) with IR application and decreased (P < 0.001) with the treatment of both antagonists. In conclusion, treatment of losartan and PD123319 played a cardioprotective role against IR injury, PD123319 being more effective in this protection.

2014 ◽  
Vol 15 (3) ◽  
pp. 241-249 ◽  
Author(s):  
Jing Hu ◽  
Zilin Li ◽  
Li-ting Xu ◽  
Ai-jun Sun ◽  
Xiao-yan Fu ◽  
...  

2008 ◽  
Vol 294 (6) ◽  
pp. H2473-H2479 ◽  
Author(s):  
Seiji Matsuhisa ◽  
Hajime Otani ◽  
Toru Okazaki ◽  
Koji Yamashita ◽  
Yuzo Akita ◽  
...  

Oxidative stress is involved in the tolerance to ischemia-reperfusion (I/R) injury. Because angiotensin II type 1 receptor blockers (ARBs) inhibit oxidative stress, there is concern that ARBs abolish the tolerance to I/R injury. Dahl salt-sensitive (DS) hypertensive and salt-resistant (DR) normotensive rats received an antioxidant, 2-mercaptopropionylglycine (MPG), or an ARB, losartan, for 7 days. Losartan and MPG significantly inhibited oxidative stress as determined by tissue malondialdehyde + 4-hydroxynoneal and increased expression of inducible nitric oxide synthase (iNOS) in the DS rat heart. However, losartan but not MPG activated endothelial nitric oxide synthase (eNOS) as assessed by phosphorylation of eNOS on Ser1177. Infarct size after 30-min left coronary artery occlusion followed by 2-h reperfusion was comparable between DS and DR rat hearts. Although MPG and losartan had no effect on infarct size in the DR rat heart, MPG but not losartan significantly increased infarct size in the DS rat heart. A selective iNOS inhibitor, 1400W, increased infarct size in the DS rat heart, but it had no effect on infarct size in the losartan-treated DS rat heart. However, a nonselective NOS inhibitor, Nω-nitro-l-arginine methyl ester, increased infarct size in the losartan-treated DS rat heart. These results suggest that losartan preserves the tolerance to I/R injury by activating eNOS despite elimination of redox-sensitive upregulation of iNOS and iNOS-dependent cardioprotection in the DS rat heart.


In Vivo ◽  
2020 ◽  
Vol 34 (5) ◽  
pp. 2507-2516 ◽  
Author(s):  
SAVAS USTUNOVA ◽  
SELCUK TAKIR ◽  
NADIM YILMAZER ◽  
HURI BULUT ◽  
DIDEM ALTINDIREK ◽  
...  

1997 ◽  
Vol 320 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Sonia Radice ◽  
Giuseppe Rossoni ◽  
Giorgio Oriani ◽  
Michael Michael ◽  
Enzo Chiesara ◽  
...  

1997 ◽  
Vol 63 (4) ◽  
pp. 1003-1011 ◽  
Author(s):  
Sonia C Nicholson ◽  
Marian Squier ◽  
David J.P Ferguson ◽  
Zsuzsanna Nagy ◽  
Stephen Westaby ◽  
...  

2016 ◽  
Vol 06 (06) ◽  
pp. 79-86
Author(s):  
Hongbin Feng ◽  
Hongli Wang ◽  
Yang Zhao ◽  
Zhinan Zheng ◽  
Sanqing Jin

2016 ◽  
Vol 62 (13) ◽  
pp. 15 ◽  
Author(s):  
R. Ghiasi ◽  
M. Mohammadi ◽  
M. Majidinia ◽  
B. Yousefi ◽  
A. Ghiasi ◽  
...  

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