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

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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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Abbreviations

LV:

Left ventricle

RV:

Right ventricle

HR:

Heart rate

CPP:

Coronary perfusion pressure

CF:

Coronary flow

SEM:

Standard error mean

SD:

Standard deviation

DM:

Diabetes mellitus

CAD:

Coronary artery disease

HF:

Heart failure

RAAS:

Renin–angiotensin system

ATII:

Angiotensin II

AT1:

Angiotensin II receptor type 1

ACE:

Angiotensin-converting enzyme

ACEI:

Angiotensin-converting enzymes inhibitor

ARBs:

Angiotensin II receptor blockers

ACE2:

Angiotensin-converting enzyme 2

PLB:

Phospholamban

SERCA:

Sarcoplasmic reticulum Ca2+ ATP-ase

STZ:

Streptozotocin

SH:

Sulfhydryl group

dp/dt max:

Maximum rate of pressure development in LV

dp/dt min:

Minimum rate of pressure development in LV

SLVP:

Systolic left ventricle pressure

DLVP:

Diastolic left ventricle pressure

HR:

Heart rate

CF:

Coronary flow

ROS:

Reactive oxygen species

NO2 − :

Nitrites

NO:

Nitric oxide

NOS:

Nitric oxide synthetase

iNOS:

Inducible nitric oxide synthetase

·ONOO− :

Peroxynitrite

O2−:

Superoxide anion radicals

H2O2 :

Hydrogen peroxide

TBARS:

Reactive thiobarbituric substances

BP:

Blood pressure

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Author information

Authors and Affiliations

  1. Clinic of Endocrinology, Military Medical Academy, Belgrade, Serbia

    Petar Ristic

  2. Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia

    Ivan Srejovic, Vladimir Zivkovic & Vladimir Lj. Jakovljevic

  3. Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Tamara Nikolic & Isidora Stojic

  4. Clinic of Ophthalmology, Military Medical Academy, Belgrade, Serbia

    Dragana Ristic

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  1. Petar Ristic
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  2. Ivan Srejovic
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  4. Isidora Stojic
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  5. Dragana Ristic
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Correspondence to Vladimir Lj. Jakovljevic.

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Ristic, P., Srejovic, I., Nikolic, T. et al. The effects of zofenopril on cardiac function and pro-oxidative parameters in the streptozotocin-induced diabetic rat heart. Mol Cell Biochem 426, 183–193 (2017). https://doi.org/10.1007/s11010-016-2890-z

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  • DOI: https://doi.org/10.1007/s11010-016-2890-z

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