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-month-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 inte grity 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., M. Mitašíková, S. Šmidová, A. Mascaliová, V. Knezl, K. Dlugošová, Ľ. Okruhlicová, P. Weismann, N. Tribulová., and Obsahuje bibliografii a bibliografické odkazy
We have examined the changes of intercellular electrical coupling protein connexin-43 (Cx43) and of PKC-ε in heart atria of diabetic rats and/or after the treatment with triiodothyronine (T3 ). Diabetes was induced in Wistar-Kyoto rats by streptozotocin (50 mg/kg, i.v.) and atria were examined after 5 (acute stage) and 10 (chronic stage) weeks. T 3 (10 μg/100 g/day) was applied via a gastric tube for the last 10 days prior to the end of the experiments to non-diabetic and to the half of diabetic rats. Expression and phosphorylated status of Cx43, as well as expression of PKC-ε , were analyzed by Western blots using mouse monoclonal anti-Cx43 and rabbit polyclonal anti-PKC-ε antibodies. We found that the Cx43 expression was significantly increased after the treatment with T3 and in the acute diabetes. Both in diabetes and after T3 treatment the phosphorylation of Cx43 isoforms was markedly suppressed compared to the non-diabetic and T3-untreated controls. Such a down-regulation was less pronounced in diabetic rats after the T3-treatment. The expression of atrial PKC-ε was increased in diabetic rats. This increase was suppressed after T3 administration and the expression was decreased in T3-treated non-diabetic rats. We suggest that the reduced Cx43 phosphorylation in diabetic and hyperthyroid rats can deteriorate a cell-to-cell coupling and consequently facilitate a development of atrial tachyarrhythmia in diabetic or hyperthyroid animals., M. Mitašíková ... [et al.]., and Obsahuje seznam literatury
For better understanding of pathophysiological processes leading to increased retention of sodium as a consequence of hyperlipidemia, the properties of renal Na,K-ATPase, a key enzyme involved in maintaining sodium homeostasis in the organism, were studied. Enzyme kinetics of renal Na,K-ATPase were used for characterization of ATP- and Na+-binding sites after administration of fish oil (FO) (30 mg · day-1) or atorvastatin (0.5 mg·100 g-1 day-1) to healthy Wistar rats and rats with hereditary hypertriglyceridemia of both genders. Untreated healthy Wistar and also hypertriglyceridemic female rats revealed higher Na,K-ATPase activity as compared to respective untreated male groups. Hypertriglyceridemia itself was accompanied with higher Na,K-ATPase activity in both genders. Fish oil improved the enzyme affinity to ATP and Na+, as indicated by lowered values of K m and K Na in Wistar female rats. In Wistar male rats FO deteriorated the enzyme in the vicinity of the Na+-binding site as revealed from the increased K Na value. In hypertriglyceridemic rats FO induced a significant effect only in females in the vicinity of the sodium binding sites resulting in improved affinity as documented by the lower value of KNa. Atorvastatin aggravated the properties of Na,K-ATPase in both genders of Wistar rats. In hypertriglyceridemic rats protection of Na,K-ATPase was observed, but this effect was bound to females only. Both treatments protected renal Na,K-ATPase in a gender specific mode, resulting probably in improved extrusion of excessive intracellular sodium out of the cell affecting thus the retention of sodium in hHTG females only., N. Vrbjar ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy