Connexin 43 expression is impaired in beginning heart failure in spontaneously hypertensive rats

Various alterations in molecular and cellular events have been considered as possibly contributing to the cardiac remodelling that occurs during the transition from compensated hypertrophy to heart failure. The aim of the present study is to clarify (1) whether cardiac apoptosis occurs during the transition from compensated hypertrophy to decompensated heart failure, and (2) whether expression of the genes encoding Bax (an apoptosis inducer) and Bcl-xL and Bcl-2 (apoptosis inhibitors) is altered during this transition. We used 12-month-old and 20-month-old male spontaneously hypertensive rats (SHR12 and SHR20 respectively) and age-matched Wistar–Kyoto rats (WKY12 and WKY20 respectively). These rats were killed after measurement of haemodynamic parameters by transthoracic echocardiography and use of a tipmanometer via the right carotid artery. The expression of bcl-2, bcl-xL and bax was analysed by Northern blotting. Samples were also fixed in 4% paraformaldehyde for in situ nick end-labelling (TUNEL) methods and immunohistochemistry. SHR12 had well compensated left ventricular hypertrophy with normal fractional shortening and normal end-systolic wall stress. In contrast, the hearts of SHR20 developed decompensated dilatation, with a decrease in fractional shortening and an increase in end-systolic wall stress. TUNEL-positive cells were seen exclusively in the hearts of SHR20. The major cell types that showed TUNEL-positive nuclei were non-cardiomyocytes. The expression of bax remained unchanged during the transition to heart failure. However, there was increased expression of bcl-xL in the failing stage, whereas the expression of bcl-2 remained unchanged. Immunohistochemical studies revealed that Bcl-xL protein was up-regulated in the hearts of SHR20. In conclusion, non-cardiomyocyte apoptosis may play a contributory role in the remodelling that occurs in the transition from compensatory hypertrophy to decompensated heart failure. In addition, it is suggested that enhanced expression of bcl-xL plays an important role in the preservation of cardiomyocytes during this transition.

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Aged male and female spontaneously hypertensive rats benefit from n-3 polyunsaturated fatty acids supplementation

Physiological Research ◽

10.33549/physiolres.931550 ◽

2008 ◽

pp. S39-S48

Author(s):

M Mitašíková ◽

S Šmidová ◽

A Macsaliová ◽

V Knezl ◽

K Dlugošová ◽

...

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Connexin 43 ◽

Spontaneously Hypertensive Rats ◽

Cell Junctions ◽

Hypertensive Rats ◽

Pufa Supplementation ◽

Male And Female ◽

Spontaneously Hypertensive ◽

Gap Junction Channel

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.

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Protein expression of myostatin and follistatin in the myocardium of spontaneously hypertensive rats with heart failure

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.1036.8 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Ricardo Luiz Damatto ◽

Paula Martinez ◽

Daniele Guizoni ◽

Aline Lima ◽

Marcelo Cezar ◽

...

Keyword(s):

Heart Failure ◽

Protein Expression ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

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Potassium Alginate Oligosaccharides Alter Gut Microbiota, and Have Potential to Prevent the Development of Hypertension and Heart Failure in Spontaneously Hypertensive Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22189823 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9823

Author(s):

Zhen-Lian Han ◽

Meng Chen ◽

Xiao-Dan Fu ◽

Min Yang ◽

Maria Hrmova ◽

...

Keyword(s):

Heart Failure ◽

Gut Microbiota ◽

Natriuretic Peptide ◽

Spontaneously Hypertensive Rats ◽

Therapeutic Potential ◽

Favorable Effect ◽

Protective Effects ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Alginate Oligosaccharides

Food-derived oligosaccharides show promising therapeutic potential in lowering blood pressure (BP), but the mechanism is poorly understood. Recently, the potential role of gut microbiota (GM) in hypertension has been investigated, but the specific GM signature that may participate in hypertension remains unclear. To test the potassium alginate oligosaccharides (PAO) mechanism in lowering BP and specific microbial signature changes in altering GM, we administered various dosages of PAO in 40 spontaneously hypertensive rats for a duration of six weeks. We analyzed BP, sequenced the 16S ribosomal DNA gene in the cecum content, and gathered RNA-seq data in cardiac tissues. We showed that the oral administration of PAO could significantly decrease systolic BP and mean arterial pressure. Transcriptome analyses demonstrated that the protective effects of developing heart failure were accompanied by down-regulating of the Natriuretic Peptide A gene expression and by decreasing the concentrations of angiotensin II and atrial natriuretic peptide in plasma. In comparison to the Vehicle control, PAO could increase the microbial diversity by altering the composition of GM. PAO could also decrease the ratio of Firmicutes to Bacteroidetes by decreasing the abundance of Prevotella and Phascolarctobacterium bacteria. The favorable effect of PAO may be added to the positive influence of the abundance of major metabolites produced by Gram-negative bacteria in GM. We suggest that PAO caused changes in GM, and thus, they played an important role in preventing the development of cardiovascular disease.

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