The effects of zofenopril on cardiac function and pro-oxidative parameters in the streptozotocin-induced diabetic rat heart

Mol Cell Biochem. 2017 Feb;426(1-2):183-193. doi: 10.1007/s11010-016-2890-z. Epub 2016 Nov 24.

Abstract

Diabetes mellitus is a chronic condition that continues to increase in both incidence and prevalence. Renin-Angiotensin-Aldosterone System is one of the main modulators of chronic hyperglycaemia and, thus, its influence on tissues. Hyperglycaemia-induced oxidative stress is an important factor in diabetic cardiomyopathy. The present study was carried out on 24 adult male Wistar albino rats (8-week-old and with body masses of 190 ± 10 g). We evaluated the influence of acute administration of zofenopril on ex vivo myocardial function from rats with streptozotocin-induced diabetes mellitus, with a special emphasis on cardiodynamic and oxidative stress parameters in diabetic rat hearts. Rats were divided randomly into two groups (12 animals per group): control non-diabetic animals (C) were healthy rats perfused with 1.5 µM of zofenopril, and STZ-treated diabetic animals (DM) were diabetic animals perfused with 1.5 µM of zofenopril 4 weeks after the induction of diabetes. Our results demonstrated that diabetic rats are characterized by a depressed cardiac performance and that oxidative markers are related to alterations in cardiac function in rats with 4 weeks of STZ-induced diabetes. Additionally, the use of zofenopril as a monotherapy slightly diminished cardiac damage induced by chronic hyperglycaemia. However, long-term follow-up intervention trials are necessary to fully demonstrate the benefit of zofenopril in this context. A challenge for future investigations will be to identify the effects of chronic administration or combination therapy with angiotensin-converting enzyme inhibitors in various models of diabetes.

Keywords: Cardiodynamics; Isolated heart; Oxidative parameter; Rat; Streptozotocin.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Captopril / analogs & derivatives*
  • Captopril / pharmacology
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Cardiomyopathies / blood
  • Diabetic Cardiomyopathies / drug therapy*
  • Diabetic Cardiomyopathies / physiopathology*
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar

Substances

  • Biomarkers
  • zofenopril
  • Captopril