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The effects of zofenopril on cardiac function and pro-oxidative parameters in the streptozotocin-induced diabetic rat heart
Authors:Petar Ristic  Ivan Srejovic  Tamara Nikolic  Isidora Stojic  Dragana Ristic  Vladimir Zivkovic  Vladimir Lj Jakovljevic
Institution:1.Clinic of Endocrinology,Military Medical Academy,Belgrade,Serbia;2.Department of Physiology, Faculty of Medical Sciences,University of Kragujevac,Kragujevac,Serbia;3.Department of Pharmacy, Faculty of Medical Sciences,University of Kragujevac,Kragujevac,Serbia;4.Clinic of Ophthalmology,Military Medical Academy,Belgrade,Serbia
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.
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