Dose-dependent protective effect of ivabradine against ischemia-reperfusion-induced renal injury in rats

Kidney Blood Press Res. 2012;35(2):114-9. doi: 10.1159/000330501. Epub 2011 Nov 1.

Abstract

Background/aims: This study was designed to investigate the dose-dependent protective effect of ivabradine, a specific inhibitor of the cardiac sinoatrial node, on renal ischemia-reperfusion (I/R) injury in rats.

Methods: Rats were divided into six groups: group 1, control; group 2, I/R (60 min ischemia followed by 24 h reperfusion); groups 3 and 4, 0.6-6 mg/kg ivabradine; and groups 5 and 6, sham+0.6-6 mg/kg ivabradine. At the end of the study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase contents were assayed in the kidney tissues; serum blood levels of urea nitrogen (BUN), creatinine (Cr) and albumin also were determined.

Results: Tissue MDA levels were found to be significantly higher in the I/R group, whereas SOD and CAT levels were lower when compared to the control group. Ivabradine (0.6 mg/kg) treatment reduced the MDA levels and elevated the SOD and CAT enzyme activity. Treatment with a dose of 6 mg/kg ivabradine further increased MDA levels and did not ameliorate SOD or CAT activities. Serum levels of BUN and Cr were significantly higher in the I/R group. I/R+0.6 mg ivabradine reduced the elevated BUN and Cr levels.

Conclusion: This study indicates that ivabradine exerts a dose-dependent response beyond heart rate reduction against renal I/R injury.

MeSH terms

  • Animals
  • Benzazepines / pharmacology*
  • Catalase / metabolism
  • Cyclic Nucleotide-Gated Cation Channels / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Female
  • Glutathione Peroxidase / metabolism
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Ivabradine
  • Kidney / drug effects
  • Kidney / enzymology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism*
  • Kidney Diseases / physiopathology
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / physiopathology
  • Sinoatrial Node / drug effects
  • Sinoatrial Node / physiology
  • Superoxide Dismutase / metabolism

Substances

  • Benzazepines
  • Cyclic Nucleotide-Gated Cation Channels
  • Ivabradine
  • Malondialdehyde
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase