Polyunsaturated omega-3 fatty acids ( ω-3 PUFA) are important components of cell membrane a ffecting its function and their deficiency is deleterious to health. We have previously shown that spontaneously hypertensive rats (SHR) are prone to life- threatening arrhythmias that are reduced by ω-3 PUFA intake. Purpose of this study was to explore plasma and red blood cells (RBC) profile of ω-3 and ω-6 PUFA as well as to determine ω-3 index, a risk factor for sudden cardiac death, in aged SHR and the effect of ω-3 PUFA intake. Male and female 12-month-old SHR and age-matched Wi star rats fed with ω-3 PUFA (200 mg/kg BW/day/2 month) were compared with untreated rats. Composition of ω-3 PUFA: alfa linolenic acid, eicosapentaenoic acid (EPA) and docosahexaen oic acid (DHA) as well as ω-6 PUFA: linoleic acid and arachidonic acid was analyzed by gas chromatography. Results showed sex- and strain-related differences of basal ω-3 and ω-6 PUFA levels in plasma and RBC as well as in response to ω-3 PUFA intake. Comparing to Wistar rats ω-3 index, expressed as a percentage of EPA+DHA of total fatty acids, was lower in SHR and it increased due to consumption of ω-3 PUFA. Findings support our hypothesis that lower ω-3 index may be also a marker of increased propensity of the hypertensive rat heart to malignant arrhythmias., B. Bačová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Previous data suggest that type 1 diabetes mellitus leads to the deterioration of myocardial intercellular communication mediated by connexin-43 (Cx43) channels. We therefore aimed to explore Cx43, PKC signaling and ultrastructure in non -treated and omega-3 fatty acid (omega-3) treated spontaneously diabetic Goto-Kakizaki (GK) rats considered as type 2 diabetes model. Four-week-old GK and non-diabetic Wistar-Clea rats were fed omega -3 (200 mg/kg/day) for 2 months and compared with untreated rats. Realtime PCR and immunoblotting were performed to determine Cx43, PKC- epsilon and PKC-delta expression. In situ Cx43 was examined by immunohistochemistry and subcellular alterations by electr on microscopy. Omega-3 intake reduced blood glucose, triglycerides, and cholesterol in diabetic rats and this was associated with improved integrity of cardiomyocytes and capillaries in the heart. Myocardial Cx43 mRNA and protein levels were higher in diab etic versus non- diabetic rats and were further enhanced by omega-3. The ratio of phosphorylated (functional) to non-phosphorylated Cx43 was lower in diabetic compared to non- diabetic rats but was increased by omega-3, in part due to up -regulation of PKC-epsilon. In addition, proapoptotic PKC-delta expression was decreased. In conclusion, spontaneously diabetic rats at an early stage of disease benefit from omega-3 intake due to its hypoglycemic effect, upregulation of myocardial Cx43, and preservation of cardiovascular ultrastructure. These findings indicates that supplementation of omega-3 may be beneficial also in the management of diabetes in humans., J. Radosinska, L. H. Kurahara, K. Hiraishi, C. Viczenczova, T. Egan Benova, B. Szeiffova Bacova, V: Dosenko, J. Navarova, B. Obsitnik, I. Imanaga, T. Soukup, N. Tribulova., and Obsahuje bibliografii
We aimed to explore the effects of melatonin and n-3 polyunsaturated fatty acids (PUFA) supplementation on plasma and aortic nitric oxide (NO) levels in isoproterenol (Iso) affected spontaneously hypertensive (SHR) and Wistar rats. Untreated control rats were compared with Iso injected (118 mg/kg, s.c.) rats, and Iso injected plus supplemented with melatonin (10 mg/kg, p.o.) or PUFA (1.68 g/kg, p.o.) for two months. Plasma and aortic basal, L-NAME inhibited, adrenaline and acetylcholine stimulated NO were determined using Griess method. Plasma NO levels were lower in SHR versus Wistar rats. Iso decreased NO in Wistar while not in SHR. PUFA but not melatonin intake of Iso treated SHR increased plasma NO along with a decrease in systolic blood pressure. Basal aortic NO level was higher in SHR than Wistar rats and not altered by Iso. Intake of melatonin increased but PUFA decreased basal NO levels in Wistar+Iso and did not affect in SHR+Iso rats. Acetylcholine and adrenaline induced aortic NO release was significantly increased in Wistar+Iso but not SHR+Iso group. Melatonin intake increased Ach induced aortic NO in Wistar+Iso and SHR+Iso groups, whereas there was no effect of PUFA intake. Findings suggest that PUFA modulates plasma and melatonin aortic NO levels of isoproterenol affected rats in a strain-dependent manner., K. K. Chaudagar, C. Viczenczova, B. Szeiffova Bacova, T. Egan Benova, M. Barancik, N. Tribulova., and Obsahuje bibliografii
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 connex in 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., N. Tribulová, V. Knezl, Ľ. Okruhlicová, J. Slezák., and Obsahuje bibliografii a bibliografické odkazy
Excessive production of oxygen free radicals has been regarded as a causative common denominator of many pathological processes in the animal kingdom. Hydroxyl and nitrosyl radicals represent the major cause of the destruction of biomolecules either by a direct reaction or by triggering a chain reaction of free radicals. Scavenging of free radicals may act preventively or therapeutically. A number of substances that preferentially react with free radicals can serve as scavengers, thus increasing the internal capacity/activity of endogenous antioxidants and protecting cells and tissues against oxidative damage. Molecular hydrogen (H2) reacts with strong oxidants, such as hydroxyl and nitrosyl radicals, in the cells, that enables utilization of its potential for preventive and therapeutic applications. H2 rapidly diffuses into tissues and cells without affecting metabolic redox reactions and signaling reactive species. H2 reduces oxidative stress also by regulating gene expression, and functions as an anti-inflammatory and anti-apoptotic agent. There is a growing body of evidence based on the results of animal experiments and clinical observations that H2 may represent an effective antioxidant for the prevention of oxidative stress-related diseases. Application of molecular hydrogen in situations with excessive production of free radicals, in particular, hydroxyl and nitrosyl radicals is relatively simple and effective, therefore, it deserves special attention., J. Slezák, B. Kura, K. Frimmel, M. Zálešák, T. Ravingerová, C. Viczenczová, Ľ. Okruhlicová, N. Tribulová., and Obsahuje bibliografii
Gap junction connexin channels are important determinants of myocardial conduction and synchronization that is crucial for coordinated heart function. One of the main risk factors for cardiovascular events that results in heart attack, congestive heart failure, stroke as well as sudden arrhythmic death is hypertension. Mislocalization and/or dysfunction of specific connexin-43 channels due to hypertension-induced myocardial remodeling have been implicated in the occurrence of lifethreatening arrhythmias and heart failure in both, humans as well as experimental animals. Recent studies suggest that downregulation of myocardial connexin-43, its abnormal distribution and/or phosphorylation might be implicated in this process. On the other hand, treatment of hypertensive animals with cardioprotective drugs (e.g. statins) or supplementation with non-pharmacological compounds, such as melatonin, omega-3 fatty acids and red palm oil protects from lethal arrhythmias. The antiarrhythmic effects are attributed to the attenuation of myocardial connexin-43 abnormalities associated with preservation of myocardial architecture and improvement of cardiac conduction. Findings uncover novel mechanisms of cardioprotective (antihypertensive and antiarrhythmic) effects of compounds that are used in clinical settings. Well-designed trials are needed to explore the antiarrhythmic potential of these compounds in patients suffering from hypertension., T. Egan Benova, B. Szeiffova Bacova, C. Viczenczova, E. Diez, M. Barancik, N. Tribulova., and Obsahuje bibliografii