<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Aim:</bold> The aim is to identify the possible changes in the expression of genes, that regulate calcium homeostasis in cardiomyocytes in diabetes mellitus.<bold>Methods:</bold> 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.<bold>Results:</bold> The expression of SERCA2a in short-term protocol was decreased. In long-term protocol, decreased SERCA2a, TRPC4 and TRPC6 mRNA levels were observed (*p &lt; 0.05). SERCA2a and TRPC4 mRNA levels exhibited statistical monotonic correlation in STZ-treated group in long-term protocol.<bold>Conclusions:</bold> 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.</abstract>

Deteriorated gene expression of selected calcium transporters in streptozotocin-induced diabetic hearts of Wistar rats

<abstract xmlns="http://www.w3.org/1999/xhtml">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 &lt; 0.05).Conclusion: NaNO3 administration affected the expression of caveolin-1 and the ratio of its active (phosphorylated) isoform increased.</abstract>

Impact of nitrate therapy on the expression of caveolin-1 and its phosphorylated isoform in lungs in the model of monocrotaline induced pulmonary hypertension

<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Background:</bold> This study specified the role of several significant ion channels regulating the metabolism of calcium ions in contraction and relaxation of human detrusor muscle in order to identify possible target for future drugs that are capable of treating diseases resulting from impaired detrusor activity, e.g. overactive bladder. Although this disease can be successfully treated with muscarinic receptor antagonists or β3 agonist, many patients may not be suitable for chronic therapy, especially due to the relatively high side effects of the treatment.<bold>Material and Methods:</bold> The study used the isolated detrusor tissue samples, which were obtained from the macroscopic healthy tissue of urinary bladder from 19 patients undergoing a total prostatectomy because of localized prostate cancer. Each biological sample was prepared into 8 strips. We used oxybutynin and mirabegron as control drugs and several blockers of specific subtypes calcium and potassium ion channels as tested substances. The contractility of bladder was investigated by an organ tissue bath method in vitro and contraction was induced by carbachol.<bold>Results:</bold> The amplitude of contraction was successfully decreased by positive control drugs and, from tested agents, the comparable effect had the substance capable of influencing IP3 receptors and Orai-STIM channels and combination consisting of drugs possessing an inhibitory effect on IP3 receptors, L- and T-type voltage-gated calcium channels and Orai-STIM channels.<bold>Conclusion:</bold> The present work represents a new finding about handling Ca2+ in urinary bladder contraction and pointed to a dominant role of IP3 receptor-mediated pathway in the regulation of Ca2+ metabolism, which may represent a future strategy in pharmacotherapy of impaired detrusor activity.</abstract>

Jessenius Faculty of Medicine in Martin (JFM CU), Biomedical Centre Martin JFM CU

Jessenius Faculty of Medicine in Martin (JFM CU), Department of Pharmacology JFM CU

The Modulation Of Detrusor Contractility By Agents Influencing Ion Channel Activity

<abstract xmlns="http://www.w3.org/1999/xhtml">The aim of this study was to determine pharmacological possibilities of influencing the risk factors of metabolic syndrome (MetS). Hypertriacylglycerolemic (HTG) rats fed with high-fat-fructose diet (HFFD) were used as a model of the MetS. Wistar rats fed with standard diet were used as negative control group. HTG rats fed with HFFD for 8 weeks were used as positive control group. The effects of atorvastatin and SMe1EC2 were tested. The compounds were administered to the HTG rats after 5 weeks of HFFD, once a day for 3 weeks. After 8 weeks, the blood serum lipid profile and electrophysiology of neurotransmission in hippocampal sections were evaluated <italic>in vitro</italic>. SMe1EC2 and atorvastatin had a significant effect on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol) and atorvastatin had a significant effect on triacylglycerols (TGs). SMe1EC2 improved the long-term potentiation (LTP) course in the hippocampus.</abstract>

Slovak Academy of Sciences, Centre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology

Effect of high-fat-fructose diet on synaptic plasticity in hippocampus and lipid profile of blood serum of rat: pharmacological possibilities of affecting risk factors

<abstract xmlns="http://www.w3.org/1999/xhtml">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.</abstract>

SDF-1 and its receptor in the ventricles of rat with monocrotaline-induced pulmonary hypertension

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European Pharmaceutical Journal

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