scholarly journals Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 546 ◽  
Author(s):  
Barbara Szeiffova Bacova ◽  
Csilla Viczenczova ◽  
Katarina Andelova ◽  
Matus Sykora ◽  
Kiranj Chaudagar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Connexin 43 ◽  
Electrical Coupling ◽  
Threshold Current ◽  
Prolonged Treatment ◽  
Diffuse Fibrosis ◽  
Omega 3 ◽  
Hypertensive Rats ◽  
Protein Levels ◽  
Coupling Protein

Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced β-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-β1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKCε, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats.

scholarly journals Cardiac Connexin-43 and PKC Signaling in Rats With Altered Thyroid Status Without and With Omega-3 Fatty Acids Intake

2016 ◽  
pp. S77-S90 ◽  
Author(s):  
B. SZEIFFOVÁ BAČOVÁ ◽  
T. EGAN BEŇOVÁ ◽  
C. VICZENCZOVÁ ◽  
T. SOUKUP ◽  
H. RAUCHOVÁ ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Thyroid Hormones ◽  
Connexin 43 ◽  
Heart Function ◽  
Electrical Coupling ◽  
Omega 3 ◽  
Thyroid Status ◽  
Pkc Epsilon ◽  
Coupling Protein ◽  
Altered Thyroid

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 T3) 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.

scholarly journals Omacor Protects Normotensive and Hypertensive Rats Exposed to Continuous Light from Increased Risk to Malignant Cardiac Arrhythmias

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 659
Author(s):  
Tamara Egan Benova ◽  
Csilla Viczenczova ◽  
Barbara Szeiffova Bacova ◽  
Jitka Zurmanova ◽  
Vladimir Knezl ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Electrical Coupling ◽  
Continuous Light ◽  
Male Rat ◽  
Human Populations ◽  
Omega 3 ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Populations At Risk ◽  
Increased Risk

Light pollution disturbs circadian rhythm, and this can also be deleterious to the heart by increased susceptibility to arrhythmias. Herein, we investigated if rats exposed to continuous light had altered myocardial gene transcripts and/or protein expression which affects arrhythmogenesis. We then assessed if Omacor® supplementation benefitted affected rats. Male and female spontaneously hypertensive (SHR) and normotensive Wistar rats (WR) were housed under standard 12 h/12 h light/dark cycles or exposed to 6-weeks continuous 300 lux light for 24 h. Half the rats were then treated with 200 mg/100 g b.w. Omacor®. Continuous light resulted in higher male rat vulnerability to malignant ventricular fibrillation (VF). This was linked with myocardial connexin-43 (Cx43) down-regulation and deteriorated intercellular electrical coupling, due in part to increased pro-inflammatory NF-κB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ATPase transcripts. Omacor® treatment increased the electrical threshold to induce the VF linked with amelioration of myocardial Cx43 mRNA and Cx43 protein levels and the suppression of NF-κB and iNOS. This indicates that rat exposure to continuous light results in deleterious cardiac alterations jeopardizing intercellular Cx43 channel-mediated electrical communication, thereby increasing the risk of malignant arrhythmias. The adverse effects were attenuated by treatment with Omacor®, thus supporting its potential benefit and the relevance of monitoring omega-3 index in human populations at risk.

Melatonin attenuates hypertension-related proarrhythmic myocardial maladaptation of connexin-43 and propensity of the heart to lethal arrhythmias

2013 ◽  
Vol 91 (8) ◽  
pp. 633-639 ◽  
Author(s):  
Tamara Benova ◽  
Csilla Viczenczova ◽  
Jana Radosinska ◽  
Barbara Bacova ◽  
Vladimir Knezl ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Wistar Rats ◽  
Electrical Coupling ◽  
Wistar Rat ◽  
Spontaneously Hypertensive ◽  
Kinase C ◽  
Rat Hearts ◽  
Cx43 Mrna ◽  
Cardioprotective Effects ◽  
Coupling Protein

We hypothesized that the pineal hormone melatonin, which exhibits cardioprotective effects, might affect myocardial expression of cell-to-cell electrical coupling protein connexin-43 (Cx43) and protein kinase C (PKC) signaling, and hence, the propensity of the heart to lethal ventricular fibrillation (VF). Spontaneously hypertensive (SHR) and normotensive Wistar rats fed a standard rat chow received melatonin (40 μg/mL in drinking water during the night) for 5 weeks, and were compared with untreated rats. Melatonin significantly reduced blood pressure and normalized triglycerides in SHR, whereas it decreased body mass and adiposity in Wistar rats. Compared with healthy rats, the threshold to induce sustained VF was significantly lower in SHR (18.3 ± 2.6 compared with 29.2 ± 5 mA; p < 0.05) and increased in melatonin-treated SHR and Wistar rats to 33.0 ± 4 and 32.5 ± 4 mA. Melatonin attenuated abnormal myocardial Cx43 distribution in SHR, and upregulated Cx43 mRNA, total Cx43 protein, and its functional phosphorylated forms in SHR, and to a lesser extent, in Wistar rat hearts. Moreover, melatonin suppressed myocardial proapoptotic PKCδ expression and increased cardioprotective PKCε expression in both SHR and Wistar rats. Our findings indicate that melatonin protects against lethal arrhythmias at least in part via upregulation of myocardial Cx43 and modulation of PKC-related cardioprotective signaling.

scholarly journals Suppression of β1-Adrenoceptor Autoantibodies is Involved in the Antiarrhythmic Effects of Omega-3 Fatty Acids in Male and Female Hypertensive Rats

2020 ◽  
Vol 21 (2) ◽  
pp. 526 ◽  
Author(s):  
Barbara Szeiffova Bacova ◽  
Jana Radosinska ◽  
Gerd Wallukat ◽  
Miroslav Barancik ◽  
Anne Wallukat ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Heart Diseases ◽  
Membrane Integrity ◽  
Omega 3 ◽  
Hypertensive Rats ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
Cell Membrane Integrity ◽  
Activity Preservation ◽  
Underlying Mechanisms

The arrhythmogenic potential of β1-adrenoceptor autoantibodies (β1-AA), as well as antiarrhythmic properties of omega-3 in heart diseases, have been reported while underlying mechanisms are poorly understood. We aimed to test our hypothesis that omega-3 (eicosapentaenoic acid-EPA, docosahexaenoic acid-DHA) may inhibit matrix metalloproteinase (MMP-2) activity to prevent cleavage of β1-AR and formation of β1-AA resulting in attenuation of pro-arrhythmic connexin-43 (Cx43) and protein kinase C (PKC) signaling in the diseased heart. We have demonstrated that the appearance and increase of β1-AA in blood serum of male and female 12-month-old spontaneously hypertensive rats (SHR) was associated with an increase of inducible ventricular fibrillation (VF) comparing to normotensive controls. In contrast, supplementation of hypertensive rats with omega-3 for two months suppressed β1-AA levels and reduced incidence of VF. Suppression of β1-AA was accompanied by a decrease of elevated myocardial MMP-2 activity, preservation of cardiac cell membrane integrity and Cx43 topology. Moreover, omega-3 abrogated decline in expression of total Cx43 as well as its phosphorylated forms at serine 368 along with PKC-ε, while decreased pro-fibrotic PKC-δ levels in hypertensive rat heart regardless the sex. The implication of MMP-2 in the action of omega-3 was also demonstrated in cultured cardiomyocytes in which desensitization of β1-AR due to permanent activation of β1-AR with isoproterenol was prevented by MMP-2 inhibitor or EPA. Collectively, these data support the notion that omega-3 via suppression of β1-AA mechanistically controlled by MMP-2 may attenuate abnormal of Cx43 and PKC-ε signaling; thus, abolish arrhythmia substrate and protect rats with an advanced stage of hypertension from malignant arrhythmias.

Exercise training improves aortic endothelium-dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertensive rats

2004 ◽  
Vol 96 (6) ◽  
pp. 2088-2096 ◽  
Author(s):  
Drew A. Graham ◽  
James W. E. Rush
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Exercise Training ◽  
Spontaneously Hypertensive Rats ◽  
No Synthase ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Endothelial No Synthase ◽  
Endothelium Dependent Relaxation

The present study examined in vitro vasomotor function and expression of enzymes controlling nitric oxide (NO) bioavailability in thoracic aorta of adult male normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) that either remained sedentary (Sed) or performed 6 wk of moderate aerobic exercise training (Ex). Training efficacy was confirmed by elevated maximal activities of both citrate synthase ( P = 0.0024) and β-hydroxyacyl-CoA dehydrogenase ( P = 0.0073) in the white gastrocnemius skeletal muscle of Ex vs. Sed rats. Systolic blood pressure was elevated in SHR vs. WKY ( P < 0.0001) but was not affected by Ex. Despite enhanced endothelium-dependent relaxation to 10-8 M ACh in SHR vs. WKY ( P = 0.0061), maximal endothelium-dependent relaxation to 10-4 M ACh was blunted in Sed SHR (48 ± 12%) vs. Sed WKY (84 ± 6%, P = 0.0067). Maximal endothelium-dependent relaxation to 10-4 M ACh was completely restored in Ex SHR (93 ± 9%) vs. Sed SHR ( P = 0.0011). Nω-nitro-l-arginine abolished endothelium-dependent relaxation in all groups ( P ≤ 0.0001) and caused equal vasocontraction to maximal ACh in Sed SHR and Ex SHR. Endothelium-independent relaxation to sodium nitroprusside was similar in all groups. Protein levels of endothelial NO synthase were higher in SHR vs. WKY ( P = 0.0157) and in Ex vs. Sed ( P = 0.0536). Protein levels of the prooxidant NAD(P)H oxidase subunit, gp91phox, were higher in SHR vs. WKY ( P < 0.0001) and were diminished in Ex vs. Sed ( P = 0.0557). Levels of the antioxidant SOD-1, -2, and catalase enzymes were lower in SHR vs. WKY (all P ≤ 0.0005) but were not altered by Ex. Thus elevated gp91phox-dependent oxidative stress and reduced antioxidant capacity likely contributed to impaired endothelium-dependent vasorelaxation in Sed SHR. Furthermore, reduced gp91phox-dependent oxidative stress and enhanced endothelial NO synthase-derived NO likely contributed to restored endothelium-dependent vasorelaxation in Ex SHR.

scholarly journals The Effects of Apitherapeutic Agents on Oxidative Stress in Serum Metabolic Parameters of Hypertensive Rats Created by Nitric Oxide Synthase Inhibited

2021 ◽  
Vol 50 (6) ◽  
pp. 1745-1754
Author(s):  
Mehmet Fuat Gulhan ◽  
Betul Ozdemir ◽  
Zeliha Selamoglu ◽  
Engin Sahna
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Total Antioxidant Status ◽  
Nuclear Factor Κb ◽  
Treated Group ◽  
Caffeic Acid Phenethyl Ester ◽  
Stress Index ◽  
Clinical Effects ◽  
Hypertensive Rats ◽  
Protein Levels

Hypertension is a chronic disease affecting the whole world due to its clinical effects and complications. The reduction in the release and effect of NO is one of the mechanisms of hypertension formation. Hypertension disrupts the balance between oxidant and antioxidant mechanisms. In this study, we aimed to observe biochemical changes in the blood by treatment propolis, caffeic acid phenethyl ester (CAPE) and pollen in hypertensive rats via Nω-Nitro-L-arginine methyl ester (L-NAME). Rats were divided in five groups. Rats were given L-NAME (40 mg/kg, intraperitoneally) for 14 days to make hypertensive. L-NAME and bee products were administered together with rats for 14 days, then L-NAME for 14 days. All administrated ended 28 days. There was a statistically significant (P<0.05) decrease in blood pressure (BP) in the groups in which bee products were applied. Blood pressure was lower in the pollen treated group than in the CAPE and propolis treated group (P<0.05). Paraoxanase (PON1), total antioxidant status (TAS), total oxidant status (TOS), asymmetric dimethylarginine (ADMA), nuclear factor-κB (NF-κB) levels were measured in the blood samples in all groups. In the L-NAME group; PON1, TAS, HDL, and total protein levels were found to be lower than the groups applied bee products (P<0.05). TOS, oxidative stress index (OSI), ADMA, NF-κB, glucose, cholesterol, LDL, triglyceride, ALT, AST, ALP levels were found to be lower in groups plus of bee products were applied compared to the group that received L-NAME (P<0.05). The results showed that oxidative stress and homeostasis can be regulated with propolis, CAPE and pollen in hypertensive rats induced L-NAME.

Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?

2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Close Association ◽  
Omega 3 ◽  
Endstage Renal Disease ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.

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