Long-lasting disturbances in lipid and glucose metabolism present in metabolic syndrome (MetS) lead to serious cardiovascular diseases. The study was aimed to evaluate the effect of natural antioxidant vitamin E (VitE, 100 mg/kg/day, p.o.) on basal biochemical and physiological parameters characterizing MetS and on the changed function of the heart. Furthermore, the possible potentiation of VitE effect by synthetic pyridoindole antioxidant SMe1EC2 (SMe, 15 mg/kg/day, p.o.) was also tested. MetS was induced in hereditary hypertriglyceridemic rats (HTG) by the 5 weeks administration of high-fat fructose diet (HFFD: 1 % cholesterol, 7.5 % pork lard, 10 % fructose). The heart function was tested using Langendorff preparation under constant pressure. The functional parameters of isolated heart, dysrhythmias and evoked fibrillations were evaluated in conditions of ischemia-reperfusion. The HFFD increased body weight gain and serum levels of total cholesterol, low-density lipoproteins and blood glucose. The HFFD significantly increased heart flow and force of contraction, compared to standard diet (SD). During the reperfusion, the HFFD caused the increase of the ventricular premature beats number at the expense of decreasing the duration of serious dysrhythmias (ventricular tachycardias and fibrillations). The addition of VitE, SMe or their combination to the HFFD decreased body weight gain, depressed blood pressure, improved particular biochemical parameters. The combination of VitE and SMe suppressed the occurrence of serious dysrhythmias. Our data indicate that the HFFD-related disturbances led to alterations within pathophysiology in HTG rats. The results showed that a combination of antioxidants might have the potential to amend disorders accompanying MetS.

• MeSH
• antioxidancia farmakologie   MeSH
• dieta s vysokým obsahem tuků MeSH
• fruktosa MeSH
• hmotnostní přírůstek MeSH
• krevní glukóza metabolismus   MeSH
• krysa rodu Rattus MeSH
• metabolický syndrom * komplikace   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• fruktosa MeSH
• krevní glukóza MeSH

Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-?B) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-?B expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.

• MeSH
• biometrie MeSH
• fruktosa škodlivé účinky   MeSH
• indoly farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• metabolický syndrom farmakoterapie   enzymologie   etiologie   MeSH
• myokard metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• potkani Wistar MeSH
• preklinické hodnocení léčiv MeSH
• pyridiny farmakologie   terapeutické užití   MeSH
• rutin farmakologie   terapeutické užití   MeSH
• srdce účinky léků   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fruktosa MeSH
• indoly MeSH
• NF-kappa B MeSH
• Nos3 protein, rat MeSH Prohlížeč
• pyridiny MeSH
• rutin MeSH
• SMe1EC2 MeSH Prohlížeč
• synthasa oxidu dusnatého, typ III MeSH

People with metabolic syndrome have higher risk of cardiovascular diseases then those without. The aim of the work was to investigate whether high fat diet administered to Prague hereditary hypertriglyceridemic (HTG) rats can induce signs of metabolic syndrome (MetS). Our results showed that HTG rats fed high fat diet (HTGch) had disturbed glucose metabolism and also lipid metabolism - increased serum triacylglycerols (TAG), total cholesterol (Ch), low-density lipoprotein-Ch (LDL-Ch), and decreased high-density lipoprotein-Ch (HDL-Ch). Their livers proved markers of developing steatosis. Moreover, HTGch had increased blood pressure, yet the vascular endothelium was not significantly damaged. All these changes were accompanied with oxidative stress and tissue damage identified as increased liver concentrations of thiobarbituric acid reactive substances (TBARS) and activity of the lysosomal enzyme N-acetyl-D-glucosaminidase (NAGA). We assume that the model used may be suitable for the study of MetS with no evidence of obesity. Prolongation of the high fat diet duration might have a major impact on all parameters tested, especially on vascular endothelial function.

• MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• HDL-cholesterol krev   MeSH
• hypertriglyceridemie krev   etiologie   MeSH
• krysa rodu Rattus MeSH
• LDL-cholesterol krev   MeSH
• metabolický syndrom krev   etiologie   MeSH
• modely nemocí na zvířatech * MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• HDL-cholesterol MeSH
• LDL-cholesterol MeSH

Thyroid hormones are powerful modulators of heart function and susceptibility to arrhythmias via both genomic and non-genomic actions. We aimed to explore expression of electrical coupling protein connexin-43 (Cx43) in the heart of rats with altered thyroid status and impact of omega-3 polyunsaturated fatty acids (omega-3) supplementation. Adult male Lewis rats were divided into following six groups: euthyroid controls, hyperthyroid (treated with T(3)) and hypothyroid (treated with methimazol) with or without six-weeks lasting supplementation with omega-3 (20 mg/100 g/day). Left and right ventricles, septum and atria were used for immunoblotting of Cx43 and protein kinase C (PKC). Total expression of Cx43 and its phosphorylated forms were significantly increased in all heart regions of hypothyroid rats compared to euthyroid controls. In contrast, the total levels of Cx43 and its functional phosphorylated forms were decreased in atria and left ventricle of hyperthyroid rats. In parallel, the expression of PKC epsilon that phosphorylates Cx43, at serine 368, was increased in hypothyroid but decreased in hyperthyroid rat hearts. Omega-3 intake did not significantly affect either Cx43 or PKC epsilon alterations. In conclusion, there is an inverse relationship between expression of cardiac Cx43 and the levels of circulating thyroid hormones. It appears that increased propensity of hyperthyroid while decreased of hypothyroid individuals to malignant arrhythmias may be in part attributed to the changes in myocardial Cx43.

• MeSH
• fosforylace MeSH
• hormony štítné žlázy krev   MeSH
• hypertyreóza metabolismus   MeSH
• hypotyreóza metabolismus   MeSH
• konexin 43 metabolismus   MeSH
• kyseliny mastné omega-3 farmakologie   MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• myokard enzymologie   MeSH
• náhodné rozdělení MeSH
• potkani inbrední LEW MeSH
• potravní doplňky MeSH
• proteinkinasa C metabolismus   MeSH
• srdce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Gja1 protein, rat MeSH Prohlížeč
• hormony štítné žlázy MeSH
• konexin 43 MeSH
• kyseliny mastné omega-3 MeSH
• matrixová metaloproteinasa 2 MeSH
• Mmp2 protein, rat MeSH Prohlížeč
• proteinkinasa C MeSH

We aimed to determine the impact of Ca(2+)-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca(2+) handling. Langedorff-perfused rat or guinea pig hearts subjected to K(+)-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca(2+) disturbances and Ca(2+) overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca(2+)](i)-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca(2+)-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias.

• MeSH
• draslík MeSH
• homeostáza MeSH
• kardiomyocyty metabolismus   ultrastruktura   MeSH
• krysa rodu Rattus MeSH
• morčata MeSH
• noradrenalin MeSH
• poruchy metabolismu vápníku komplikace   patologie   MeSH
• prasata MeSH
• srdeční arytmie etiologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• morčata MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• draslík MeSH
• noradrenalin MeSH

Direct cell-to-cell communication in the heart is maintained via gap junction channels composed of proteins termed connexins. Connexin channels ensure molecular and electrical signals propagation and hence are crucial in myocardial synchronization and heart function. Disease-induced gap junctions remodeling and/or an impairment or even block of intercellular communication due to acute pathological conditions results in derangements of myocardial conduction and synchronization. This is critical in the development of both ventricular fibrillation, which is a major cause of sudden cardiac death and persistent atrial fibrillation, most common arrhythmia in clinical practice often resulting in stroke. Many studies suggest that alterations in topology (remodeling), expression, phosphorylation and particularly function of connexin channels due to age or disease are implicated in the development of these life-threatening arrhythmias. It seems therefore challenging to examine whether compounds that could prevent or attenuate gap junctions remodeling and connexin channels dysfunction can protect the heart against arrhythmias that cause sudden death in humans. This assumption is supported by very recent findings showing that an increase of gap junctional conductance by specific peptides can prevents atrial conduction slowing or re-entrant ventricular tachycardia in ischemic heart. Suppression of ischemia-induced dephosphorylation of connexin seems to be one of the mechanisms involved. Another approach for identifying novel treatments is based on the hypothesis that even non-antiarrhythmic drugs with antiarrhythmic ability can modulate gap junctional communication and hence attenuate arrhythmogenic substrates.

• MeSH
• antiarytmika terapeutické užití   MeSH
• fibrilace komor farmakoterapie   metabolismus   MeSH
• fibrilace síní farmakoterapie   metabolismus   MeSH
• fosforylace MeSH
• konexin 43 metabolismus   MeSH
• lidé MeSH
• mezerový spoj účinky léků   metabolismus   patologie   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• myokard metabolismus   patologie   MeSH
• srdeční arytmie farmakoterapie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antiarytmika MeSH
• konexin 43 MeSH

Thyroid hormones (TH) are powerful modulators of heart function, but their arrhythmogenic effects are less elucidated. We have examined both acute and long-term action of TH on the heart susceptibility to the ventricular fibrillation (VF) and on the heart ability to terminate VF and restore a sinus rhythm. Triiodothyronine (T3) was applied in the range of 10(-9)-10(-6) mol/l in acute experiments using isolated perfused aged (14-month-old) guinea pig hearts. L-thyroxine (T4) was applied in the dose of 50 microg/100g/day to young (3-month-old) and aged (20-month-old) rats for 2 weeks. The T4 treatment resulted in an increased susceptibility of young, but not adult rat hearts to a hypokalemia-induced VF and facilitated a spontaneous sinus rhythm (SSR) restoration in the latter group. The acute T3 administration in the range of 10(-9)-10(-7) mol/l significantly decreased the susceptibility of an isolated heart to an electrically induced VF and also facilitated the sinus rhythm restoration. The SSR restoration was, however, not affected by 10(-6) mol/l concentration of T3, which also led to an increased VF susceptibility. Results indicate that TH can affect the susceptibility of the heart to VF and its ability to restore the sinus rhythm via acute (non-genomic) and long-term (genomic) actions. Furthermore, an anti- and pro-arrhythmic potential of TH appears to be age- and dose-dependent.

• MeSH
• časové faktory MeSH
• fibrilace komor metabolismus   patofyziologie   prevence a kontrola   MeSH
• kardiomyocyty metabolismus   patologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• morčata MeSH
• potkani Wistar MeSH
• převodní systém srdeční patofyziologie   MeSH
• srdeční frekvence MeSH
• thyroxin aplikace a dávkování   metabolismus   MeSH
• trijodthyronin aplikace a dávkování   metabolismus   MeSH
• věkové faktory MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• morčata MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• thyroxin MeSH
• trijodthyronin MeSH

Hypertension-induced myocardial metabolic, structural and electrophysiological remodeling deteriorates with aging and contributes to both heart failure and occurrence of malignant arrhythmias. It has been shown in clinical trials that n-3 polyunsaturated fatty acids (n-3 PUFA) reduce the incidence of cardiovascular diseases and sudden cardiac death. We investigated the cardioprotective effects of n-3 PUFA in aged spontaneously hypertensive rats (SHR) and possible cellular mechanisms involved. Male and female 14-moth-old SHR were fed with n-3 PUFA (Vesteralens, Norway, 20 mg/day for two months) and compared with untreated SHR. Results showed that n-3 PUFA supplementation led to 1) significant decline of blood pressure; 2) suppression of inducible ventricular fibrillation (VF) by 57 % (male) and 67 % (female), although the arrhythmogenic substrates, like fibrosis, hypertrophy and abnormal gap junctions distribution were not eliminated; 3) preservation of the cardiomyocytes and the integrity of their junctions; 4) enhancement of energetic metabolism enzyme activity; 5) augmentation of capillary density associated with increased alkaline phosphatase and decreased dipeptidyl peptidase-4 (DPP4) activity and 6/ increase in gap junction channel connexin-43 expression. Thus, aged male as well as female SHR benefit from n-3 PUFA supplementation that results in decrease in VF susceptibility, partly due to an improvement of myocardial metabolic state, cardiomyocyte and cell-to-cell junctions integrity and Cx43 up-regulation.

• MeSH
• energetický metabolismus účinky léků   MeSH
• fibrilace komor etiologie   metabolismus   patofyziologie   prevence a kontrola   MeSH
• hypertenze komplikace   farmakoterapie   metabolismus   patofyziologie   MeSH
• kapiláry účinky léků   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• konexin 43 metabolismus   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• kyseliny mastné omega-3 farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• myokard enzymologie   metabolismus   patologie   MeSH
• potkani inbrední SHR MeSH
• potravní doplňky * MeSH
• těsný spoj účinky léků   metabolismus   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• konexin 43 MeSH
• kyseliny mastné omega-3 MeSH

The contrasting pattern of cardiac inotropy induced by human peptide endothelin-1 (ET-1) has not been satisfactorily explained. It is not clear whether ET-1 is primarily responsible for increased myocardial ET-1 expression and release with resultant inotropic effects, or for the induction of myocardial hypertrophy and heart failure. There are at least two subtypes of endothelin receptors (ET(A) and ET(B)) and the inotropic effects of ET-1 differ depending on the receptor involved. Along with some other groups, we reported significant subtype-ET(B) endothelin receptor down-regulation in human cardiac cells preincubated with endothelin agonists (Drímal et al. 1999, 2000). The present study was therefore designed to clarify the subtype-selective mechanisms underlying the inotropic response to ET-1 and to its ET(B)-selective fragment (8-21)ET-1 in the isolated rat heart. The hearts were subjected to (1-21)ET-1 and to (8-21)ET-1, or to 30 min of stop-flow ischemia followed by 40 min of reperfusion, both before and after selective blockade of endothelin receptors. The present study revealed that both peptides, ET-1 and its (8-21)ET-1 fragment, significantly reduced coronary blood flow in nmolar and higher concentrations. The concomitant negative inotropy and chronotropy were marked after ET-1, while the infusion of the ET-1(8-21) fragment produced a slight but significant positive inotropic effect. Among the four endothelin antagonists tested in continuous infusion only the non-selective PD145065 and ET(B1/B2) selective BQ788 (in molar concentrations) slightly reduced the early contractile dysfunction of the heart induced by ischemia, whereas ET(A)-selective PD155080 partially protected the rat heart on reperfusion.

• MeSH
• dioxoly farmakologie   MeSH
• endotelin-1 analogy a deriváty   antagonisté a inhibitory   chemie   farmakologie   MeSH
• endoteliny farmakologie   MeSH
• funkce levé komory srdeční účinky léků   fyziologie   MeSH
• ischemická choroba srdeční patofyziologie   prevence a kontrola   MeSH
• komorový tlak (srdce) účinky léků   fyziologie   MeSH
• kontrakce myokardu účinky léků   fyziologie   MeSH
• koronární cirkulace účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• oligopeptidy farmakologie   MeSH
• peptidové fragmenty farmakologie   MeSH
• perfuze MeSH
• piperidiny farmakologie   MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu patofyziologie   prevence a kontrola   MeSH
• sekvence aminokyselin MeSH
• srdce účinky léků   fyziologie   patofyziologie   MeSH
• srdeční frekvence účinky léků   fyziologie   MeSH
• srdeční selhání etiologie   patofyziologie   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BQ 788 MeSH Prohlížeč
• dioxoly MeSH
• endotelin-1 MeSH
• endoteliny MeSH
• endothelin-1 (1-21) MeSH Prohlížeč
• oligopeptidy MeSH
• PD 145065 MeSH Prohlížeč
• PD 155080 MeSH Prohlížeč
• peptidové fragmenty MeSH
• piperidiny MeSH
• sovateltide MeSH Prohlížeč

In acute experiments on anaesthetized dogs, the haemodynamic effect of etacizine (0.5 and 1.0 mg.kg-1 i.v.) and lidocaine (2.5 and 10 mg.kg-1 i.v.) were compared. Etacizine produced a decrease in heart rate and a temporary decrease in myocardial contractility. After the dose of 1 mg.kg-1 there occurred a temporary increase in peripheral vascular resistance. It did not affect aortal blood pressure, systolic and minute output volume of the heart. Lidocaine produced a decrease in heart rate, aortal blood pressure, systolic and minute output cardiac volume with a rapid return to the original values. Besides this negative effect it was possible to observe an increase in the minute output volume and peripheral vascular resistance with larger doses, which gives evidence of the central effect of the drug.

• MeSH
• antiarytmika farmakologie   MeSH
• fenothiaziny farmakologie   MeSH
• hemodynamika účinky léků   MeSH
• intravenózní infuze MeSH
• lidokain aplikace a dávkování   farmakologie   MeSH
• psi MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiarytmika MeSH
• ethacizine MeSH Prohlížeč
• fenothiaziny MeSH
• lidokain MeSH