Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril

Jasenovec, Tomáš; Radošinská, Dominika; Kollárová, Marta; Bališ, Peter; Dayar, Ezgi; Bernátová, Iveta; Zórad, Štefan; Vrbjar, N; Cacanyova, Sona; Radošinská, Jana

doi:10.3390/biomedicines9121902

Cited by 4 publications

(3 citation statements)

References 52 publications

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“…Carbonyl stress was measured based on the concentration of advanced glycation end products (AGEs). Detailed information on the procedures has been provided elsewhere (Jasenovec, Radosinska, Kollarova, Balis, Dayar et al., 2021). The protein concentration was determined by the bicinchoninic acid kit, according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

ZDF (fa/fa) rats show increasing heterogeneity in main parameters during ageing, as confirmed by biometrics, oxidative stress markers and MMP activity

Kollárová

Chomová

Radošinská

et al. 2022

Experimental Physiology

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Zucker diabetic fatty [ZDF (fa/fa)] rats, which are an animal model for the study of type 2 diabetes, are considered as a uniform group in most experimental studies; however, there are indications of their increasing inhomogeneity over time. The main objective of our study was to monitor biometric and biochemical parameters of ZDF (fa/fa) rats during their development of type 2 diabetes and compare them with two control strains [Wistar and lean ZDF (fa/+) rats]. According to fasting glycaemia, ZDF (fa/fa) rats were split arbitrarily into two phenotypes: obese, ZDF (fa/fa) FAT; and diabetic, ZDF (fa/fa) DIA. Glycaemia increased progressively only in the ZDF (fa/fa) DIA animals, which also exhibited higher cholesterol levels compared with ZDF (fa/fa) FAT animals. In addition, ZDF (fa/fa) FAT rats revealed more pronounced left ventricular hypertrophy and higher body weight, differentiating them from ZDF (fa/fa) DIA rats.We also investigated the activity of matrix metalloproteinases (MMPs), which are multifunctional enzymes involved in tissue remodelling. Rats in the ZDF (fa/fa) FAT group revealed lower plasma MMP2 and MMP9 activity compared with the ZDF (fa/fa) DIA group. However, increased myocardial MMP2 activity indicated left ventricular remodelling in both ZDF phenotypes. Given that type 2 diabetes in humans is a heterogeneous metabolic disorder, the heterogeneity of ZDF (fa/fa) rats might be beneficial in the study of different aspects of this pathology. Moreover, Wistar rats could serve as a more appropriate control for aged ZDF (fa/fa) rats than the commonly used ZDF fa/+ rats, which showed an increase in left ventricular weight, carbonyl stress markers in the left myocardium and MMP2 activity in both ventricles, indicating heart remodelling processes compared with the Wistar control group.

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Section: Methodsmentioning

confidence: 99%

ZDF (fa/fa) rats show increasing heterogeneity in main parameters during ageing, as confirmed by biometrics, oxidative stress markers and MMP activity

Kollárová

Chomová

Radošinská

et al. 2022

Experimental Physiology

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“…Measurements of ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC) were used as markers of antioxidant status. TAC measurements were carried out as described previously [ 61 ].…”

Section: Methodsmentioning

confidence: 99%

Monocrotaline-Induced Pulmonary Arterial Hypertension and Bosentan Treatment in Rats: Focus on Plasma and Erythrocyte Parameters

et al. 2022

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The objective of our study was to contribute to the characterization of monocrotaline-induced pulmonary arterial hypertension (PAH) in a rat model, with emphasis on the renin–angiotensin–aldosterone system, parameters of oxidative stress, the activity of matrix metalloproteinases, and erythrocyte parameters. Moreover, we aimed to analyze the effects of bosentan. Experiments were performed on 12-week-old male Wistar rats randomly assigned to 3 groups: control, monocrotaline-treated (60 mg/kg), and monocrotaline combined with bosentan (300 mg/kg/day). Our study confirmed the well-known effects of monocrotaline administration on lungs and the right ventricle, as well as pulmonary arterial pressure. In addition, we observed activation of the alternative pathway of the renin–angiotensin system, namely an increase in angiotensin (Ang) 1–7 and Ang 1-5 together with an increase in Ang I, but without any change in Ang II level, and downregulation of aldosterone 4 weeks after monocrotaline administration. For the first time, modifications of erythrocyte Na,K-ATPase enzyme kinetics were demonstrated as well. Our observations do not support data obtained in PAH patients showing an increase in Ang II levels, increase in oxidative stress, and deterioration in RBC deformability. Although bosentan primarily targets the vascular smooth muscle, our study confirmed its antioxidant effect. The obtained data suggest that besides the known action of bosentan, it decreases heart rate and increases erythrocyte deformability, and hence could have a beneficial hemodynamic effect in the PAH condition.

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“…The Synergy H1 Hybrid Multi-mode multi-detection microplate reader (Agilent, Santa Clara, CA, USA) was used for spectrophotometric and fluorometric measurements, while all reagents were obtained from Sigma-Aldrich (Steinheim, Germany). All the above methods were described in detail previously [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

Na,K-ATPase Kinetics and Oxidative Stress in Kidneys of Zucker Diabetic Fatty (fa/fa) Rats Depending on the Diabetes Severity—Comparison with Lean (fa/+) and Wistar Rats

Vrbjar

Jasenovec

Kollárová

et al. 2022

Biology

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For a better insight into relations between type 2 diabetes mellitus (T2DM) and Na,K-ATPase properties in kidneys, we aimed to characterize two subgroups of ZDF obese (fa/fa) rats, with more and less developed T2DM, and compare them with two controls: lean (fa/+) and Wistar. Na,K-ATPase enzyme kinetics were estimated by measuring the ATP hydrolysis in the range of NaCl and ATP levels. As Na,K-ATPase is sensitive to oxidative stress, we evaluated selected oxidative stress parameters in kidney homogenates. Our results suggest that thiol–disulfide redox balance in the renal medulla and Na,K-ATPase properties in the renal cortex differ between both controls, while observed measurements in lean (fa/+) rats showed deviation towards the values observed in ZDF (fa/fa) rats. In comparison with both controls, Na,K-ATPase enzyme activity was higher in the renal cortex of ZDF rats independent of diabetes severity. This might be a consequence of increased glucose load in tubular fluid. The increase in lipid peroxidation observed in the renal cortex of ZDF rats was not associated with Na,K-ATPase activity impairment. Regarding the differences between subgroups of ZDF animals, well-developed T2DM (glycemia higher than 10 mmol/L) was associated with a higher ability of Na,K-ATPase to utilize the ATP energy substrate.

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Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril

Cited by 4 publications

References 52 publications

ZDF (fa/fa) rats show increasing heterogeneity in main parameters during ageing, as confirmed by biometrics, oxidative stress markers and MMP activity

ZDF (fa/fa) rats show increasing heterogeneity in main parameters during ageing, as confirmed by biometrics, oxidative stress markers and MMP activity

Monocrotaline-Induced Pulmonary Arterial Hypertension and Bosentan Treatment in Rats: Focus on Plasma and Erythrocyte Parameters

Na,K-ATPase Kinetics and Oxidative Stress in Kidneys of Zucker Diabetic Fatty (fa/fa) Rats Depending on the Diabetes Severity—Comparison with Lean (fa/+) and Wistar Rats

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