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.

Autonomic responses of the insular cortex in hypertensive and normotensive rats

1995 ◽  
Vol 268 (1) ◽  
pp. R214-R222 ◽  
Author(s):  
K. S. Butcher ◽  
D. F. Cechetto
Keyword(s):  
Wistar Rats ◽  
Spontaneously Hypertensive Rat ◽  
Focal Cerebral Ischemia ◽  
Insular Cortex ◽  
Cardiovascular Effects ◽  
Wistar Rat ◽  
Homocysteic Acid ◽  
Spontaneously Hypertensive ◽  
Pressor Responses ◽  
Acute Changes

Lesion and focal cerebral ischemia of the insular cortex (IC) results in elevated renal sympathetic nerve activity (RSNA) and arterial pressure (AP) in the Wistar rat, while the opposite effect is observed in the spontaneously hypertensive rat (SHR). Acute changes in AP, heart rate (HR) and RSNA were measured in propofol-anesthetized and conscious SHR (n = 17) and Wistar rats (n = 17) during pressure injection of D,L-homocysteic acid (DLH; 100 mM) and lidocaine (LID; 20 mg/ml) into the IC. DLH injections (200 nl) into the IC of anesthetized Wistar rats resulted in a significant increase in MAP (mean change = +27 +/- 7 mmHg; P < 0.05) and a significant decrease in HR (-22 +/- 9 beats/min) and RSNA (-11 +/- 4 microV.s). Neither DLH nor LID injections into the IC of anesthetized SHR affected MAP or RNA. DLH and LID injections (500 nl) into the IC of conscious Wistar rats both resulted in a significant increase in MAP (+26 +/- 5 mmHg; 11 +/- 4 mmHg, respectively). Neither DLH nor LID injections had any cardiovascular effects in the conscious SHR. It therefore appears that the IC of conscious Wistar rats has a tonic inhibitory output, while neural excitation is capable of eliciting pressor responses. Conversely, the IC of SHR appears to exert no tonic influence on MAP.

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 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 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.

Up-regulation of myocardial connexin-43 in spontaneously hypertensive rats fed red palm oil is most likely implicated in its anti-arrhythmic effects

2012 ◽  
Vol 90 (9) ◽  
pp. 1235-1245 ◽  
Author(s):  
Barbara Bačová ◽  
Jana Radošinská ◽  
Csilla Viczenczová ◽  
Vladimír Knezl ◽  
Victor Dosenko ◽  
...  
Keyword(s):  
Palm Oil ◽  
Connexin 43 ◽  
Spontaneously Hypertensive Rat ◽  
Cell Communication ◽  
Spontaneously Hypertensive ◽  
Red Palm Oil ◽  
Wky Rats ◽  
Treatment Dose ◽  
Cx43 Mrna ◽  
Wistar Kyoto

The purpose of this study was to test our hypothesis that red palm oil (RPO) intake may affect abnormalities of myocardial connexin-43 (Cx43) and protein kinase Cε (PKCε) signaling, and consequently the propensity of the spontaneously hypertensive rat heart (SHR) heart to arrhythmias. SHR and Wistar–Kyoto (WKY) rats fed a standard rat chow plus red palm oil (200 µL/day) for 5 weeks were compared with untreated rats. Cytosolic but not particulate PKCε expression as well as Cx43-mRNA, total Cx43 proteins, and its phoshorylated forms were increased, and disordered localization of Cx43 was attenuated in the left ventricle of RPO-fed SHR compared with untreated rats. These alterations were associated with suppression of early post-ischemic-reperfusion-related ventricular tachycardia and electrically inducible ventricular fibrillation. However, the treatment dose of RPO caused down-regulation of myocardial Cx43, but did not alter its cell membrane distribution or overall PKCε expression in WKY rats. It was, however, associated with poor arrhythmia protection, suggesting overdosing. Results indicate that SHR benefit from RPO intake, particularly because of its apparent anti-arrhythmic effects. This protection can be, in part, attributed to the preservation of cell-to-cell communication via up-regulation of myocardial Cx43, but not with PKCε activation.

Myocardial connexin-43 is upregulated in response to acute cardiac injury in rats

2017 ◽  
Vol 95 (8) ◽  
pp. 911-919 ◽  
Author(s):  
Csilla Viczenczova ◽  
Branislav Kura ◽  
Kiranj K. Chaudagar ◽  
Barbara Szeiffova Bacova ◽  
Tamara Egan Benova ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Subcutaneous Injection ◽  
Connexin 43 ◽  
Wistar Rats ◽  
Cardiac Injury ◽  
Rat Hearts ◽  
Heart Injury ◽  
Chest Irradiation ◽  
Intercellular Channel ◽  
Malignant Arrhythmias

We aimed to explore whether myocardial intercellular channel protein connexin-43 (Cx43) along with PKCε and MMP-2 might be implicated in responses to acute cardiac injury induced by 2 distinct sublethal interventions in Wistar rats. Animals underwent either single chest irradiation at dose of 25 Gy or subcutaneous injection of isoproterenol (ISO, 120 mg/kg) and were compared with untreated controls. Forty-two days post-interventions, the hearts were excised and left ventricles were used for analysis. The findings showed an increase of total as well as phosphorylated forms of myocardial Cx43 regardless of the type of interventions. Enhanced phosphorylation of Cx43 coincided with increased PKCε expression in both models. Elevation of Cx43 was associated with its enhanced distribution on lateral surfaces of the cardiomyocytes in response to both interventions, while focal areas of fibrosis without Cx43 were found in post-ISO but not post-irradiated rat hearts. In parallel, MMP-2 activity was decreased in the former while increased in the latter. Cardiac function was maintained and the susceptibility of the hearts to ischemia or malignant arrhythmias was not deteriorated 42 days after interventions when compared with controls. Altogether, the findings indicate that myocardial Cx43 is most likely implicated in potentially salutary responses to acute heart injury.

Surface epithelial ultrastructure of the polycystic ovary in the BB wistar rat

1986 ◽  
Vol 44 ◽  
pp. 252-253
Author(s):  
R. C. Kaufmann ◽  
F. K. Khosho ◽  
K. S. Amankwah
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Wistar Rats ◽  
Polycystic Ovary ◽  
Wistar Rat ◽  
Polycystic Ovaries ◽  
Chemical Diabetes ◽  
Scanning Electron

Diabetes decreases the fertility of females, but the mechanisms are not completely understood. In our investigations, we have found that 13% of the female BB Wistar rats that spontaneously developed chemical diabetes had persistent estrous. In this study the ovaries of these rats were examined by scanning electron microscopy(SEM) and compared to normal-cycling controls as well as to rats that had developed polycystic ovaries(PCO) by exposure to constant 1ight.

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