Aliskiren protects against myocardial ischaemia-reperfusion injury via an endothelial nitric oxide synthase dependent manner.
Aliskiren, a direct renin inhibitor, has shown potent ability to attenuate hypertension. Our previous research has found that aliskiren protected against myocardial ischaemia-reperfusion (I/R) injury and enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) in spontaneously hypertensive rats. However, whether the cardioprotective effect of aliskiren against myocardial I/R injury was eNOS-dependent is unknown. In the present study, 12-week-old male eNOS knockout (eNOS-/-) and wild-type C57BL/6J mice (WT) were orally administrated with the dose of 50 mg/kg per day of aliskiren. After a 4-week treatment, aliskiren decreased blood pressure in eNOS-/-mice, and reduced renin-angiotension II levels in both eNOS-/-and WT mice. Aliskiren also improved left ventricular ejection fraction (EF) and fractional shortening (FS), decreased myocardial infarct size, reduced creatine kinase (CK) and lactate dehydrogenase (LDH) activity in plasma, attenuated dihydroethidium (DHE) fluorescence and levels of malondialdehyde (MDA), enhanced superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) in myocardium, increased SOD and thioredoxin (Trx) proteins expression in WT mice subjected to 30 minutes of ischaemia followed by reperfusion for 24 hours. However, aliskiren failed to restore all of the above indices in eNOS-/-mice subjected to the same I/R injury. Our study indicated that aliskiren protected against myocardial I/R injury via an eNOS dependent manner.
Department of Anaesthesia, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yu
Y
Chen
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China.|Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Guoliang
G
Meng
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Wenli
W
Bai
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Yan
Y
Ma
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Liping
L
Xie
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Naila
N
Altaf
Department of Anaesthesia, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yanning
Y
Qian
Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yi
Y
Han
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Yong
Y
Ji
D000577:Amides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005650:Fumarates / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects
D000577:Amides; D002316:Cardiotonic Agents; D005650:Fumarates; C446481:aliskiren; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
endothelial nitric oxide synthase; myocardial ischaemia/reperfusion injury; oxidant stress; renin angiotensin system inhibitors