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As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia-reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10 mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os. After the treatment, hemodynamic measurements, echocardiography and assessment of myocardial function were performed according to Langendorff's retrograde perfusion method. The induced global ischemia model involved 20 min of ischemia followed by 30 min of reperfusion to the heart (I20:R30). Markers of oxidative stress were determined spectrophotometrically from plasma and erythrocyte lysates. Heart and kidney tissue samples were pathohistologically analyzed. Treatment with a combination of ACE inhibitors and diuretics significantly lowered blood pressure in spontaneously hypertensive rats, alleviated left ventricular hypertrophy and increased ejection fraction. On the other hand, treatment with zofenopril and diuretics showed pro-oxidative potential. Pathohistological analysis of heart and kidney tissue samples indicates that subchronic administration of antihypertensive agents does not lead to significant changes in these organs. Since the antihypertensive therapy was relatively short (only 4 weeks), in order to elucidate or deny the prooxidative mechanism, additional studies of a longer time interval are needed and planned., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The University of Kragujevac in Serbia’s Faculty of Medical Sciences conducted this inquiry (approval number 01-10667/1). The study procedure was carried out in compliance with the European Council Directive (86/609/EEC) and the ethical guidelines established by the faculty’s ethical committee for laboratory animal welfare. Disclaimer: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion (PFE) in ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. The first part of the study aimed to determine the dose of 10% perfluoroemulsion (PFE) that would show the best cardioprotective effect in rats on ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFE, the animals were divided into a control or experimental group. They were also grouped depending on the applied dose (8, 12, 16 ml/kg body weight) of saline or PFE. We observed the huge changes in almost all parameters in the PFE groups in comparison with IR group without any pre-treatment. Calculated in percent, dp/dt max was the most changed parameter in group treated with 8 mg/kg, while the dp/dt min, SLVP, DLVP, HR, and CF were the most changed in group treated with 16 mg/kg 10 h before ischemia. The effects of 10% PFE are more pronounced if there is a longer period of time from application to ischemia, i.e., immediate application of PFE before ischemia (1 h) gave the weakest effects on the change of cardiodynamics of isolated rat heart. Therefore, the future of PFE use is in new indications and application methods, and PFE can also be referred to as antihypoxic and antiischemic blood substitute with mild membranotropic effects., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study was aimed to examine the influence of acclimatization on the change of concentration of stress hormones in men's serum exposed to heat stress during physical training. The study included a total of 40 men, aged 19-21 years, divided randomly into four groups: CTRL group: control, exposed to the Exercise Tolerance Testing in comfortable conditions; O group: exposed to Exercise Tolerance Testing in a warm environment; P group: exposed to passive acclimation to heat for 10 days, followed by Exercise Tolerance Testing in a warm environment; A group: exposed to active acclimation to heat for 10 days, followed by Exercise Tolerance Testing in a warm environment. All participants were tested for thermoregulation and acclimatization, skin and tympanic temperature, heart rate (HR), hormonal status and sweating. The mean skin temperature was the lowest in the control group of subjects exposed to physical exertion under comfortable conditions, and at each point of measurement it was statistically significantly different from that of the other study groups (p < 0.001). Sweating intensity was statistically significantly the lowest in the CTRL group (0.32 ± 0.04 l/m 2 /h; p < 0.001), compared to all other groups. Cortisol was significantly altered in O group (632.2 ± 92.3; 467.2 ± 89.7), testosterone levels were significantly altered in P (19.2 ± 9.3; 16.4 ± 7.3) and in A groups (22.1 ± 12.4; 14.9 ± 9.9), while prolactin was changed in O (392.1 ± 51.3; 181.4 ± 42.3), P (595.1 ± 191.1; 191.2 ± 52.5), and A group (407.4 ± 189.3; 173.4 ± 43.9) after the experimental period. The impact of acclimatization on hormonal indicators emphasizes its importance in the response of the endocrine system of soldiers to perform military activities in warm climates., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

It is well known the use of ketamine and etomidate in clinical practice; however, the difference in the systemic effects of these two anesthetic agents is still debatable. Thus, in the present study we aimed to compare their effects on heart, and other organs through estimation of cardiodynamics, biochemical and hematological parameters. Male Wistar rats were divided in 2 groups containing of 2 subgroups (n = 7 in each subgroup, n = 28 in total): (1) bolus injection of anesthetic ketamine (40 mg/kg b.w., i.p. n = 14); (2) bolus injection of anesthetic etomidate (20 mg/kg b.w., i.p. n = 14). The experiments were done in vitro in one subgroup of each group: cardiodynamic variables (dp/dt max , dp/dt min , heart rate), coronary flow, oxidative stress in coronary effluent and cardiac tissue homogenate, and in vivo in another subgroup: biochemical and hematological parameters, and oxidative stress in haemolysate. Significantly increased left ventricular contractility (dp/dt max ) and relaxation (dp/dt min ) were noticed in etomidate group. Creatinine (CREA), HDL cholesterol and folate were significantly higher in etomidate group, whereas amylase (AMY) and eosinophils in ketamine group. Our results suggested that ketamine has more antioxidant potential compared to etomidate, and etomidate has more favorable effects regarding cardiac performance.

The present study aimed to estimate the effects of high-protein diet (PD)-isolated whey protein and omega-3 fatty acids-docosahexaenoic and eicosapentaenoic acid on oxidative parameters of rats treated with Olanzapine (OLZ). Experiments were carried out on 8-week-old Wistar albino male rats (n = 64) weighing 200 ± 20 g. By dietary and pharmacological treatment, all animals were divided into 8 groups: 1. CTRL group; 2. CTRL + OLZ group; 3. CTRL + FA group; 4. CTRL + OLZ + FA group; 5. PD group; 6. PD + OLZ group; 7. PD + FA group; 8. PD + OLZ + FA group. After 6 weeks of pharmacological/diet treatment, all animals were sacrificed to collect blood samples and determine the biomarkers of oxidative stress. The following oxidative stress markers were measured spectrophotometrically: superoxide anion radical (O 2 - ), hydrogen peroxide (H 2 O 2 ), nitric oxide (NO - ), index of lipid peroxidation measured as TBARS, reduced glutathione, catalase and superoxide dismutase. The study has shown that Olanzapine treatment was associated with increased release of pro-oxidants and diminished activity of anti-oxidant markers. Additional supplementation with PD and FA succeeded in abolishing the negative influence in most of the measured parameters. However, these beneficial impacts were stronger in the case of their separate application, which could be the practical and clinical importance of these results.

This study investigated different dietary strategies, high-fat (HFd), or standard diet (Sd) alone or in combination with standardized Aronia melanocarpa extract (SAE), as a polyphenol-rich diet, and their effects on lipids and fatty acids (FA) in rats with metabolic syndrome (MetS). Wistar albino rats were randomly divided into two groups: healthy and rats with MetS, and then depending on dietary patterns on six groups: healthy rats fed with Sd, healthy rats fed with Sd and SAE, rats with MetS fed with HFd, rats with MetS fed with HFd and SAE, rats with MetS fed with Sd, and rats with MetS fed with Sd and SAE. 4 weeks later, after an overnight fast (12-14 h), blood for determination of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), index of lipid peroxidation (measured as TBARS), and FA was collected. Increased FA and lipid concentration found in MetS rats were reduced when changing dietary habits from HFd to Sd with or without SAE consumption. Consumption of SAE slightly affects the FA profiles, mostly palmitoleic acid in healthy rats and PUFA in MetS + HFd rats. Nevertheless, in a high-fat diet, SAE supplementation significantly decreases n-6/n-3 ratio, thereby decreasing systemic inflammation. Further researches are warranted to confirm these effects in humans.

This study was aimed to assess the impact of aerobic and anaerobic type of exercise on blood pressure and redox status in normotensive and hypertensive rats. After 1 week of preconditioning feeding and 1 week of preconditioning running regimen, Wistar albino rats (n = 72; bw: 270 ± 50 g) were randomly assigned to three groups according to running protocol (high-intensity interval training (HIIT) or moderate-intensity training (MIT)): sedentary control, MIT, HIIT; spontaneous hypertensive sedentary control (SHR), SHR + MIT and SHR + HIIT. Blood pressure (BP) measurement was performed by a tail-cuff noninvasive method BP system. After 48 h of rest following the final training, the rats were fasted for 24 h and sacrificed under ketamine/xylazine anesthesia and blood samples were collected. The level of the next prooxidants were measured: superoxide anion radical (O 2 - ); hydrogen peroxide (H 2 O 2 ); nitrite level (NO 2 - ) and index of lipid peroxidation (thiobarbituric acid reactive substances), and the activity of antioxidative enzymes: reduced glutathione (GSH) superoxide dismutase (SOD) and catalase (CAT) activity. After the last week of running, HIIT strongly affected SP, DP, and HR in SHR rats compared to other hypertensive rats, as well as after MIT in normotensive conditions. We have found that HIIT training protocol induced a higher increase of O 2 - and H 2 O 2 as compared to MIT. Findings of the present study pointed out that contrary to normotensive conditions, in hypertensive conditions both training regimes reduced the BP levels, which was more prominent in case of HIIT. In addition, MIT seems to be connected with milder disturbance of pro-oxidant production and better antioxidant response.

The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representative of the mitochondrial ATP-dependent potassium (K ATP ) channel opener to cardiac contractility, coronary flow, and oxidative stress markers on ischemia/reperfusion injury in the isolated rat heart. The hearts of adult male Wistar albino rats (n = 60 total, 12 per group) were divided into five groups, two controls (preconditioning with Krebs-Henseleit solution) and three experimental depending on acute administrated pharmacological agents (0,63 µmol/L of verapamil, 0,1 µmol/L of amlodipine, and 200 µmol/L of nicorandil). After stabilization and 5 min of preconditioning in experimental groups, hearts from I/R control and all experimental groups underwent global ischemia (20 min) and reperfusion (30 min). Hearts from sham group were continuously followed for 50 min, after stabilization period. Cardiodynamic parameters and coronary flow were recorded at the end of stabilization (S), at the last minute of pharmacological preconditioning (P) and at intervals of 5 min after global ischemia, during reperfusion, or in case of sham group during 20-50 min after stabilization. At the same intervals, we collected coronary venous effluent from which we spectrophotometrically measured the parameters of oxidative stress: the index of lipid peroxidation, superoxide anion radical, hydrogen peroxide, and nitrite. In summary, our findings clearly indicate that the blocking of the calcium channel or the activation of K ATP may mediate the protective effect of myocardial preconditioning. The ex vivo results showed that all examined drugs after ischemia and reperfusion have beneficial cardioprotective properties associated with lower values of major pro-oxidative molecules. Obtained effects seem to be the most convincible in case of nicorandil.