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
Genetic component represents an important factor in the development of hypertension, which is known to be associated with changes in expression of vascular gap junction protein connexin 43 (Cx43). The aim of the study was to examine the distribution and expression of Cx43 in the aortic endothelium of adult normotensive Wistar rats (W), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR). Rings of the thoracic aorta were processed for immunofluorescence and Western blot analysis of endothelial Cx43 and for electron microscopy. Both, BHR and SHR exhibited significantly increased blood pressure vs. W (132±2 mm Hg and 185±3 mm Hg vs. 110±2 mm Hg). Reduced Cx43 immunofluorescence was observed in the endothelium of BHR and these alterations were more pronounced in SHR. Western blot analysis showed significant suppression of Cx43 expression in the aorta of both BHR (p<0.05) and SHR (p<0.001) vs. W. Electron microscopy revealed local subcellular alterations of interendothelial connections in BHR including extended tight junctions. These alterations were more frequent and marked in SHR. The results indicate that connexin 43 expression is reduced in the aortic endothelium already in prehypertensive period, which may affect cell-to-cell communication and thus participate in acceleration of hypertensive disease., K. Dlugošová, M. Mitašíková, I. Bernátová, P. Weismann, Ľ. Okruhlicová., and Obsahuje bibliografii a bibliografické odkazy
Genetic predisposition and social stress may represent important risk factors in etiology of hypertension associated with endothelial dysfunction. Perturbations of endothelial structural integrity are also critical for the pathogenesis of vascular diseases. We examined effect of chronic social stress on structure of aortic endothelium in bord erline hypertensive (BHR) and normotensive Wistar rats. Male BHR – offspring of Wistar mothers and SHR fathers and age-matched W were exposed to 6-week crowding stress (5 rats/cage, 200 cm2/rat). Aortic tissue was processed for electron microscopy and NO synthase activity measurement. Crowding stress significantly increased blood pressure in BHR compared to basal values (140±3 mm Hg vs. 130±3 mm Hg, p<0.05) and reduced enzyme activity by 37 % (p<0.01) in the aorta of BHR. Local slight structural alterations of endothelium were found in non-stressed BHR (p<0.001) when compared with Wistar rats. Chronic stress caused marked (p<0.005) subcellular injury of endothelial cells in aorta of BHR characterized by mitochondrial damage, presence of vacuoles, increased number of lysosomes, Weibel-Palade bodies, changes of intercellular connections and local disruption of endothelium, while only slight changes were seen in Wistar rats. Results suggest increased sensitivity of aortic endothelium of BHR to chronic crowding that may contribute to acceleration of arterial dysfunction., Ľ. Okruhlicová, K. Dlugošová, M. Mitašíková, I. Bernátová., and Obsahuje bibliografii a bibliografické odkazy