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Open access

P. Potucek, M. Radik, G. Doka, E. Kralova, P. Krenek and J. Klimas


Blood pressure (BP) rhythm is exhibited in a circadian pattern regulated by complex system of endogenous factors. Administration of pharmacological treatment at the right time can influence the efficacy of treatment; but while kidneys play significant role in BP regulation, little is known about their role in chronopharmacotherapy. This study aimed to compare differences between morning and evening dosing with valsartan and amlodipine combination in both short-term and long-term settings and to elucidate the role of kidneys in chronopharmacology. Spontaneously hypertensive rats aged between 8 and 10 weeks were daily treated with 10mg/kg of valsartan and 4 mg/kg of amlodipine, either in the morning or in the evening with treatment duration of 1 and 6 weeks. After short-term treatment, only morning treatment group demonstrated significantly better outcomes in terms of BP control when compared to placebo. After long-term treatment, both treatment groups gained superior results in BP control against placebo; however, no significant difference was seen between morning and evening treatment. Interestingly, clock gene expression in kidney has been significantly modulated only in the evening-treated groups, with treatment intensifying the reduced Bmal1 levels, while Per2 expression was less altered. However, no direct relation with the outcomes of the therapy has been observed, suggesting that pharmacotherapy may serve as an independent modulator of peripheral circadian clock in the kidney.

Open access

M. Dragún, G. Dóka, M. Máťuš, P. Křenek and J. Klimas


Aim: The aim is to identify the possible changes in the expression of genes, that regulate calcium homeostasis in cardiomyocytes in diabetes mellitus.

Methods: Male Wistar rats were randomized into two experimental protocols: short-term 5-days streptozotocin-induced diabetes protocol with 20 weeks old animals at the end of the protocol (total N = 20) and long-term 4-weeks protocol with 18 weeks of age at the end of the protocol (total N = 38). 50 mg/kg of streptozotocin (STZ) was administered in both protocols by a single intraperitoneal injection in 0,1M citrate buffer (pH = 4.5). Control group (CON) received only vehiculum. Gene expressions in samples of left heart ventricle were measured by RT-qPCR method.

Results: The expression of SERCA2a in short-term protocol was decreased. In long-term protocol, decreased SERCA2a, TRPC4 and TRPC6 mRNA levels were observed (*p < 0.05). SERCA2a and TRPC4 mRNA levels exhibited statistical monotonic correlation in STZ-treated group in long-term protocol.

Conclusions: In diabetes mellitus, the calcium homeostasis in cardiomyocytes is altered and there could be a relation between alteration of internal sarcoplasmatic stores and store-operated calcium entry.

Open access

M. Radik, G. Doka, E. Malikova, P. Krenek and J. Klimas


Aim: The aim of this study is to identify a possible damage to heart ventricles caused by supraphysiological doses of testosterone, voluntary physical activity or their combination.

Methods: In the 8-week long experiment, 10-12 weeks old male Wistar rats were administered testosterone depot in dose of 100 mg/kg (TES, n = 15) or vehiculum (CON, n = 12) once a week subcutaneously. Next groups injected with testosterone (SPOTES, n = 12) or vehiculum (SPO, n = 12) were running in exercise wheels ad libitum. Gene expressions in left and right ventricles of the heart were measured by quantitative reverse transcription polymerase chain reaction method.

Results:ln left ventricles of the testosterone groups, we observed a mild but significant increase in the percentage of Myh6 myosin heavy chain isoform and higher expression of NADPH oxidase subunit Cybb (*p < 0.05).

Conclusions:Testosterone affected the expression of genes related to contractile apparatus and oxidative stress in the left ventricle but not in right ventricle of the heart of rats. The observed level of physical activity did not have a compelling effect on the expression of measured genes.

Open access

J. Veteskova, M. Obsivan, Z. Kmecova, M. Radik, J. Srankova, E. Malikova, J. Klimas and P. Krenek


Aim: Chemokine stromal cell derived factor-1 (SDF-1) plays an important role in many processes such as apoptosis, proliferation, migration and angiogenesis, and these effects are mediated mostly by the receptor CXCR4. The aim of this study was to determine the expression of SDF-1 and CXCR4 in the ventricles of rats with monocrotaline-induced pulmonary hypertension.

Methods: 10–12 weeks old male Wistar rats were injected with monocrotaline (s. c., 60mg/kg; MON) or vehicle (CON). Rats were sacrificed 1 week (1W-MON, 1W-CON), 2 weeks (2W-MON, 2W-CON) and 4 weeks after monocrotaline administration (4W-MON, 4W-CON). Gene expression of SDF-1 and CXCR4 was determined by qRT-PCR.

Results: We observed a decrease in the SDF-1 expression on mRNA level in the right ventricle in 2W-MON and 4W-MON rats without any changes in the left ventricles and a decrease in CXCR4 expression in 1W-MON in both ventricles with an increase of CXCR4 expression in 4W-MON in the left ventricle (*P ˂ 0.05).

Conclusion: SDF-1/CXCR4 axis is affected in both ventricles of rats with monocrotaline model of pulmonary hypertension.

Open access

Z. Kmecova, E. Malikova, B. Zsigmondova, M. Radik, J. Veteskova, M. Marusakova, P. Krenek and J. Klimas


Aim: Nitric oxide signalling pathway showed to be one of the crucial factors in the treatment and pathogenesis of pulmonary arterial hypertension. The aim of this study was to determine the effect of administration of inorganic nitrate, NaNO3, on the expression of caveolin-1 and its phosphorylated isoform (pTyr14Cav-1) in lungs in the experimental model of monocrotaline induced pulmonary hypertension.

Methods: 10 weeks old male Wistar rats were subcutaneously injected with 60 mg/kg dose of monocrotaline (MCT) or vehicle (CON). Twelve days after the injection, part of the MCT group was receiving 0.3 mM NaNO3 (MCT+N0.3) daily in the drinking water and rest was receiving 0.08% NaCl solution. Four weeks after MCT administration, the rats were sacrificed in CO2. Protein expression in lungs was determined by western blot.

Results: We observed a significant decrease in the caveolin-1 expression and a significant shift towards the expression of pTyr14Cav-1 in the group treated with nitrate (p < 0.05).

Conclusion: NaNO3 administration affected the expression of caveolin-1 and the ratio of its active (phosphorylated) isoform increased.