There is a great urgency of detecting and monitoring myocardial fibrosis in clinical practice with the aim to improve and personalize therapy against cardiac remodelling. Hence, the aim of this study was to describe alterations in and show potential correlations between the structural characteristics and the molecular and biochemical markers of cardiac remodelling on a model of isoproterenol-induced heart failure. Two groups of 3-month-old male Wistar rats (n = 8 per group) were sacrificed after four weeks of treatment: control (placebo), ISO (5 mg/kg/day intraperitoneally). Chronic ISO treatment led to heart failure (HF) characterized by significant reduction of systolic blood pressure (SBP) accompanied by an increase in left ventricular weight (LVW) along with increased collagen content in the LV. The collagen content correlated negatively with SBP (R = -0.776, P < 0.001) and positively with LVW (R = 0.796, P < 0.001), with Col1a1 (0.83; P < 0.001) and Acta2 (0.73; P < 0.01). Moreover, the mRNA expression of fibrotic remodelling indicator, i.e. TGF-β1 tended to increase, while the level of fibrinolysis markers (MCP-1, TIMP-2, MMP) were unchanged. The plasma markers of collagen, procollagen I C-terminal propeptide (PICP) was 37.34 ± 7.10 pg/mL in control and was reduced by 42% (P < 0.05) in the ISO group and procollagen III N-terminal propeptide (PIIINP) was 1216.7 ± 191.0 pg/mL in control and was decreased by 66% (P < 0.05) in the ISO group. Surprisingly, there was no positive correlation between plasma markers of collagen, i.e. PICP and PIIINP and collagen content or molecular markers of collagen. However, both PICP and PIIINP correlated with BW (R = 0.712, resp. 0.803, P < 0.001), which was significantly reduced (by 25%, P < 0.05) in the ISO group. In conclusion, we assume that the collagen content of the left ventricle does not need unavoidably correlate with plasma markers of collagen, which might be affected by confounding factors in heart failure, such as loss of body weight, presumably associated with a catabolic condition.
- MeSH
- isoprenalin MeSH
- kolagen metabolismus MeSH
- krevní tlak MeSH
- peptidové fragmenty krev MeSH
- potkani Wistar MeSH
- prokolagen krev MeSH
- remodelace komor * MeSH
- srdeční komory metabolismus MeSH
- srdeční selhání chemicky indukované metabolismus patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cardiovascular pathologies are frequently associated with anxiety and other behavioral disturbances. Ivabradine, an inhibitor of the hyperpolarization-activated cyclic nucleotide-gated channels in the sinoatrial node, decreases heart rate and provides cardiovascular protection. Although ivabradine is increasingly used in cardiovascular medicine, the data on its behavioral effects are lacking. The aim of this work was to show ivabradine's potential effect on behavior in healthy and hypertensive rats. After a four-week treatment period, systolic blood pressure was increased in the N(G)-nitro-L-arginine methyl ester (L-NAME)-group and ivabradine significantly reduced it. Furthermore, it reduced the heart rate in both the control and L-NAME-group. In the control group, ivabradine enhanced the time spent in and transition to the open arms of the elevated plus maze test (EPM). In the L-NAME-group, ivabradine does not show a significant effect on the time spent in the EPM open arms and the number of transitions into them. Furthermore, ivabradine has no impact on cognitive function in both control and L-NAME groups. We conclude that ivabradine showed no undesirable effects on anxiety, locomotion or learning; in fact, some of these parameters were even improved. For the first time it has been shown that ivabradine is a safe cardiovascular drug regarding its effect on psycho-behavioral manifestations.
- MeSH
- hypertenze chemicky indukované farmakoterapie patofyziologie MeSH
- inhibitory enzymů farmakologie terapeutické užití MeSH
- ivabradin farmakologie terapeutické užití MeSH
- krevní tlak účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- NG-nitroargininmethylester toxicita MeSH
- paměť účinky léků fyziologie MeSH
- potkani Wistar MeSH
- srdeční frekvence účinky léků fyziologie MeSH
- úzkost * patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cardiovascular diseases including hypertension are often associated with behavioural alterations. The aim of this study was to show, whether ivabradine, the blocker of If-channel in sinoatrial node, is able to modify the behaviour of rats in L-nitro-arginine methyl ester (L-NAME)-induced hypertension and to compare the effect of ivabradine with captopril and melatonin. 12-week-old male Wistar rats were divided into the following groups: controls, ivabradine (10 mg/kg/24 h), L-NAME (40 mg/kg/24 h), L-NAME + ivabradine, L-NAME + captopril (100 mg/kg/24 h), L-NAME + melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff method once a week. The behaviour of rats was investigated during 23-hours in the phenotyper after four weeks of the treatment. Chronic administration of L-NAME induced hypertension without a change in HR. All tested substances partly prevented the increase of SBP, while ivabradine and melatonin also reduced HR. Ivabradine, captopril and melatonin reduced daily food intake, slightly decreased daily water intake and attenuated body weight gain. In L-NAME group, locomotor activity was enhanced by ivabradine, whereas exploratory behaviour was increased by melatonin and captopril. In conclusion, ivabradine, besides its potentially protective hemodynamic actions, does not seem to exert any disturbing effects on behaviour in L-NAME-induced hypertension in rats, while some of its effects were similar to captopril or melatonin. It is suggested that ivabradine used in cardiovascular indications is harmless regarding the effect on behaviour.
- MeSH
- antihypertenziva farmakologie MeSH
- benzazepiny farmakologie MeSH
- chování zvířat účinky léků MeSH
- hypertenze farmakoterapie metabolismus MeSH
- inhibitory ACE farmakologie MeSH
- kaptopril farmakologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- lokomoce účinky léků MeSH
- melatonin farmakologie MeSH
- NG-nitroargininmethylester metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- srdeční frekvence účinky léků MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Doxorubicin is a recognized chemotherapeutic agent widely employed in human malignancies. The limiting factor of its use is a number of side effects. The aim of this work was to show, whether administration of doxorubicin could induce behavioral disturbances in rats, and whether angiotensin-converting enzyme inhibitor captopril or melatonin can modify these potential alterations. DESIGN AND METHODS: Four groups of 3-month-old Wistar rats (twelve per group) were treated for 4 weeks: control (placebo-treated), doxorubicin (DOX) (5mg/kg i.v. in a single intravenous dose), DOX rats treated with either melatonin (10mg/kg/24h) or captopril (100mg/kg/24h). Systolic blood pressure (SBP) and the level of oxidative stress were investigated and behavioral tests of anxiety-open field test (OF), elevated plus maze (EPM) and light-dark box (LDB) were accomplished. RESULTS: Doxorubicin increased significantly systolic blood pressure and parameters of oxidative stress. Moreover, doxorubicin enhanced the level of anxiety in the tests of OF, EPM, and LDB. Captopril and melatonin prevented the blood pressure rise and the enhancement of oxidative load. Importantly, both substances reduced the parameters of anxiety. CONCLUSION: Chronic administration of captopril or melatonin has shown anxiolytic effect in the model of doxorubicin-induced anxiety. It does not seem unreasonable to suppose that this protective effect of captopril or melatonin against anxiety development might have been related to the antioxidative effects of both substances.
- MeSH
- antagonismus léků MeSH
- antibiotika antitumorózní farmakologie MeSH
- biologické markery metabolismus MeSH
- chování zvířat účinky léků MeSH
- doxorubicin farmakologie MeSH
- kaptopril farmakologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- melatonin farmakologie MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- arginin farmakologie terapeutické užití MeSH
- finanční podpora výzkumu jako téma MeSH
- hypertenze chemicky indukované MeSH
- krysa rodu rattus MeSH
- remodelace komor účinky léků MeSH
- synthasa oxidu dusnatého antagonisté a inhibitory účinky léků MeSH
- ubichinon diagnostické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- aorta thoracica účinky léků MeSH
- finanční podpora výzkumu jako téma MeSH
- hypertenze diagnóza MeSH
- krevní tlak účinky záření MeSH
- melatonin farmakologie MeSH
- modely nemocí na zvířatech MeSH
- NG-nitroargininmethylester farmakologie MeSH
- oxid dusnatý nedostatek MeSH
- potkani inbrední SHR MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
