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

Phenylbutyrate (PB) acts as chemical chaperone and histone deacetylase inhibitor, which is used to decrease ammonia in urea cycle disorders and has been investigated for use in the treatment of a number of lethal illnesses. We performed in vivo and in vitro experiments to examine the effects of PB on glutamine (GLN), branched-chain amino acid (BCAA; valine, leucine and isoleucine) and protein metabolism in rats. In the first study, animals were sacrificed one hour after three injections of PB (300mg/kg b.w.) or saline. In the second study, soleus (SOL, slow twitch) and extensor digitorum longus (EDL, fast twitch) muscles were incubated in a medium with or without PB (5 mM). L-[1-(14) C] leucine was used to estimate protein synthesis and leucine oxidation, and 3-methylhistidine release was used to evaluate myofibrillar protein breakdown. PB treatment decreased GLN, BCAA and branched-chain keto acids (BCKAs) in blood plasma, decreased BCAA and increased GLN concentrations in muscles, and increased GLN synthetase activities in muscles. Addition of PB to incubation medium increased leucine oxidation (55% in EDL, 29% in SOL), decreased BCKA and increased GLN in medium of both muscles, increased GLN in muscles, decreased protein synthesis in SOL and increased proteolysis in EDL. It is concluded that PB decreases BCAA, BCKA and GLN in blood plasma, activates BCAA catabolism and GLN synthesis in muscle and exerts adverse effects on protein metabolism. The results indicate that BCAA and GLN supplementation is needed when PB is used therapeutically and that PB may be a useful prospective agent which could be effective in management of maple syrup urine disease.

• MeSH
• fenylbutyráty farmakologie   MeSH
• glutamin metabolismus   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• leucin metabolismus   MeSH
• oxidace-redukce účinky léků   MeSH
• potkani Wistar MeSH
• proteosyntéza účinky léků   MeSH
• svalové proteiny metabolismus   MeSH
• techniky tkáňových kultur MeSH
• větvené aminokyseliny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Endotoxin administration is frequently used as a model of systemic inflammatory response which is considered the important pathogenetic factor in muscle wasting development in severe illness, such as sepsis, cancer, injury, AIDS and others. The main purpose of this study was determining the effect of various doses of endotoxin on protein and amino acid metabolism in two types of rat skeletal muscle. Sepsis was induced by intraperitoneal administration of endotoxin in a dose of 1, 3 and 5 mg/kg body weight (bw); control animals received a corresponding volume of the saline solution. After 24 h, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated and used for determination of total and myofibrillar proteolysis, protein synthesis, activity of cathepsins B and L, chymotrypsin-like activity of proteasome and amino acid release. The endotoxemia induced the body weight loss, the rise of total cholesterol and triglyceride plasma concentration and the protein catabolic state in skeletal muscle, which was caused by a higher increase in protein breakdown (due to activation of the proteasome system) than protein synthesis. The more significant effect of endotoxin was seen in EDL than SOL. The dose of 5 mg of endotoxin/kg bw induced the most significant changes in parameters of the protein and amino acid metabolism measured and could be therefore considered appropriate for studies of protein catabolism in young rat skeletal muscle at 24 h after endotoxin treatment.

• MeSH
• endotoxiny farmakologie   MeSH
• kathepsin B metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• krysa rodu rattus MeSH
• myofibrily metabolismus   MeSH
• potkani Wistar MeSH
• proteasomový endopeptidasový komplex metabolismus   MeSH
• sepse metabolismus   MeSH
• svalové proteiny metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of the study was to evaluate time course and dose dependence of peroxidative damage induced by tert-butyl hydroperoxide (tBHP) in rat hepatocytes cultured in suspension and in monolayer. At the lowest (0.1 mM) concentration, decrease of cytosolic glutathione and discharge of mitochondrial membrane potential (MMP) could be detected. Significant increases in leakage of lactate dehydrogenase and in malondialdehyde concentrations together with decrease of pyruvate-dependent respiration were detected at higher tBHP concentrations (above 0.5 mM) and after longer periods of incubation. Changes in plasma membrane integrity were observed at 1 mM concentration of tBHP. Succinate-dependent oxidation was most resistant to peroxidative damages. Opening of the mitochondrial permeability transition pore was responsible for the discharge of mitochondria membrane potential. In the presence of cyclosporine A and succinate, the membrane potential could be restored. Our data showed that the most sensitive indicators of the peroxidative damage are changes of cytosolic glutathione concentration and MMP.

• MeSH
• cytosol metabolismus   účinky léků   MeSH
• financování organizované MeSH
• glutathion metabolismus   MeSH
• hepatocyty metabolismus   účinky léků   MeSH
• jaterní mitochondrie enzymologie   fyziologie   účinky záření   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• L-laktátdehydrogenasa metabolismus   MeSH
• malondialdehyd metabolismus   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• oxidační stres účinky léků   fyziologie   MeSH
• oxidancia toxicita   MeSH
• peroxidace lipidů účinky léků   MeSH
• potkani Wistar MeSH
• spotřeba kyslíku účinky léků   MeSH
• terc-butylhydroperoxid toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone.

• MeSH
• antagonisté mineralokortikoidních receptorů farmakologie   terapeutické užití   MeSH
• arginin farmakologie   terapeutické užití   MeSH
• hypertenze chemicky indukované   komplikace   farmakoterapie   metabolismus   patofyziologie   MeSH
• hypertrofie levé komory srdeční farmakoterapie   etiologie   metabolismus   patofyziologie   MeSH
• kolagen metabolismus   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• myokard metabolismus   patologie   MeSH
• NG-nitroargininmethylester MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Wistar MeSH
• remodelace komor účinky léků   MeSH
• spironolakton farmakologie   terapeutické užití   MeSH
• spontánní remise MeSH
• svalové proteiny metabolismus   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND/AIMS: Growth hormone (GH) could have the potential to improve protein metabolism in sepsis but glutamine deficiency has been reported after GH treatment. The aim was to investigate the effects of glutamine deficiency in sepsis with and without GH treatment on protein and amino acid metabolism. METHODS: Cecal ligation and puncture (CLP) was used as a model of sepsis. Serious glutamine deficiency was induced by administration of glutamine synthetase inhibitor, methionine sulfoximine (MSO). Young Wistar rats were divided into 5 groups: control; CLP; CLP+MSO; CLP+GH, and CLP+MSO+GH. Parameters of protein metabolism were measured on incubated soleus and extensor digitorum longus muscles: [1-14C]leucine was used to estimate protein synthesis and leucine oxidation, tyrosine release was used to evaluate protein breakdown. Amino acid concentrations in plasma, skeletal muscle and incubation media were measured by HPLC. RESULTS/CONCLUSIONS: A reduced muscle glutamine concentration after MSO treatment is not associated with changes in the rates of protein synthesis or breakdown. MSO treatment decreased glutamine release from skeletal muscle and plasma glutamine concentration. Severe glutamine deficiency in GH-treated septic rats resulted in increased release of branched-chain amino acids from skeletal muscle. Copyright 2006 S. Karger AG, Basel.

• MeSH
• aminokyseliny metabolismus   MeSH
• financování organizované MeSH
• glutamin analýza   metabolismus   nedostatek   MeSH
• kosterní svaly metabolismus   MeSH
• krysa rodu rattus MeSH
• náhodné rozdělení MeSH
• potkani Wistar MeSH
• růstový hormon farmakologie   MeSH
• sepse metabolismus   patofyziologie   MeSH
• svalové proteiny metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH