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 ◽  
...  

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.

2008 ◽  
pp. S39-S48
Author(s):  
M Mitašíková ◽  
S Šmidová ◽  
A Macsaliová ◽  
V Knezl ◽  
K Dlugošová ◽  
...  

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-moth-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 integrity 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.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2305
Author(s):  
Wan-Ju Yeh ◽  
Jung Ko ◽  
Wei-Yi Cheng ◽  
Hsin-Yi Yang

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group’s systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.


2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Milena Menezes Amorim ◽  
Jaci Airton Castania ◽  
Helio Cesar Salgado ◽  
Valéria Paula Sassoli Fazan

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Ellen E. Gillis ◽  
Krystal N. Brinson ◽  
Olga Rafikova ◽  
Wei Chen ◽  
Jacqueline B. Musall ◽  
...  

We previously published that female spontaneously hypertensive rats (SHR) have significantly greater nitric oxide (NO) bioavailability and NO synthase (NOS) enzymatic activity in the renal inner medulla (IM) compared with age-matched males, although the mechanism responsible remains unknown. Tetrahydrobiopterin (BH4) is a critical cofactor required for NO generation, and decreases in BH4 as a result of increases in oxidative stress have been implicated in the pathogenesis of hypertension. As male SHR are known to have higher levels of oxidative stress compared with female SHR, we hypothesized that relative BH4 deficiency induced by oxidative stress in male SHR results in lower levels of NOS activity in renal IM compared with females. Twelve-week-old male and female SHR were randomized to receive tempol (30 mg/kg/day via drinking water) or vehicle for 2 weeks. Tempol treatment did not affect blood pressure (BP) in either sex, but reduced peroxynitrite levels only in males. Females had more total biopterin, dihydrobiopterin (BH2), and BH4 levels in renal IMs than males, and tempol treatment eliminated these sex differences. Females had greater total NOS activity in the renal IM than males, and adding exogenous BH4 to the assay increased NOS activity in both sexes. This sex difference in total NOS and the effect of exogenous BH4 were abolished with tempol treatment. We conclude that higher oxidative stress in male SHR results in a relative deficiency of BH4 compared with females, resulting in diminished renal NOS activity in the male.


Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 956 ◽  
Author(s):  
Tamil Selvi Sundaram ◽  
Carlotta Giromini ◽  
Raffaella Rebucci ◽  
Antonella Baldi

Marine and plant-based omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are widely added to animal diets to promote growth and immunity. We tested the hypothesis that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and their 1:2 combination could counteract acute or long-term damage of lipopolysaccharides (LPS), dextran sodium sulphate (DSS) and hydrogen peroxide (H2O2) in Intestinal Porcine Epithelial Cell line-J2 (IPEC-J2). The results showed that 24 h treatment with EPA or DHA exhibited proliferative effects in IPEC-J2 cells at low to moderate concentrations (6.25–50 μM) (p < 0.05). Further, 24 h pretreatment with individual DHA (3.3 µM), EPA (6.7 µM) or as DHA:EPA (1:2; 10 µM) combination increased the mitochondrial activity or cell membrane integrity post-LPS (24 h), DSS (24 h) and H2O2 (1 h) challenge (p < 0.05). Additionally, DHA:EPA (1:2, 10 µM) combination decreased the apoptotic caspase-3/7 activity around twofold after 24 h LPS and DSS challenge (p < 0.05). Our study confirms the proliferative and cytoprotective properties of EPA and DHA in IPEC-J2 cells. Increased intracellular mitochondrial activity and cell membrane integrity by ω-3 PUFAs can play a role in preventing enterocyte apoptosis during acute or chronic inflammatory and oxidative stress.


2010 ◽  
Vol 347 (1-2) ◽  
pp. 163-173 ◽  
Author(s):  
Jana Radosinska ◽  
Barbara Bacova ◽  
Iveta Bernatova ◽  
Jana Navarova ◽  
Anna Zhukovska ◽  
...  

1982 ◽  
Vol 101 (1) ◽  
pp. 154-160 ◽  
Author(s):  
Yoshiko Masubuchi ◽  
Toshio Kumai ◽  
Akiyo Uematsu ◽  
Kenji Komoriyama ◽  
Masanao Hirai

Abstract. Adult male and female spontaneously hypertensive rats (SHR-Okamoto, Kyoto) were gonadectomized when they were 17 weeks old. Intact SHR showed a progressive increase of their blood pressure with growth, attaining systolic pressure levels of 194–208 in males and 163–173 mmHg in females when they were 29–30 weeks old. During this same period, the gonadectomized animals showed a significant reduction in blood pressure ranging from 168–175 in males and from 158–163 mmHg in females. These studies indicate that male and female SHR gonadectomized at 17 weeks of age do not show the progressive blood pressure rise that occurs in intact SHR. There was no change in heart rate in either sex. Corticosterone (B) levels in plasma were increased in the orchidectomized males, and 18-OH-DOC levels in plasma were increased in the adrenal glands of ovariectomized females indicating that these hormonal changes probably do not play a role in SHR hypertension. It appears that gonadal and other hormones are involved in the pathogenesis of SHR hypertension.


1988 ◽  
Vol 454 (1-2) ◽  
pp. 238-243 ◽  
Author(s):  
Seizo Sadoshima ◽  
Yasuo Nakatomi ◽  
Kenichiro Fujii ◽  
Hiroaki Ooboshi ◽  
Takao Ishitsuka ◽  
...  

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