Beneficial effects of tolvaptan on atrial remodeling induced by chronic intermittent hypoxia in rats

Zhang, Kai; Ma, Zuowang; Wang, Weiding; Liu, Ruimeng; Zhang, Yue; Yuan, Meng; Li, Guangping

doi:10.1111/1755-5922.12466

Cited by 21 publications

(19 citation statements)

References 27 publications

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“… 19 Goudis and Ketikoglou 20 described that obstructive sleep apnea was associated with AF, which may implicate the pathophysiological mechanisms of AF. In addition, Zhang et al 21 showed that the percentage of the atrial collagen fraction in the CIH group was significantly increased compared with the values recorded in the control and intervention groups. Therefor, we created an atrial fibrosis model by CIH for further experimentation in this study.…”

Section: Discussionmentioning

confidence: 93%

<p>The Potential Effects of Aliskiren on Atrial Remodeling Induced by Chronic Intermittent Hypoxia in Rats</p>

Song¹,

Yu²,

Li³

et al. 2020

DDDT

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Purpose Atrial remodeling takes part in the pathogenesis of atrial fibrillation (AF). Aliskiren, as a direct renin inhibitor, has been shown to exert protective effects against arrhythmia. The aim of this study was to investigate the potential role of aliskiren in atrial remodeling in a chronic intermittent hypoxia (CIH) rat model. Methods A total of 45 Sprague–Dawley rats were randomly assigned into three groups (n=15 per group): control group; CIH group; and CIH with aliskiren (CIH-A) group. CIH and CIH-A rats were subjected to CIH for 6 h per day for 4 weeks. Atrial fibrosis was evaluated using Masson’s trichrome staining. Electrophysiological tests were conducted in the isolated perfused hearts to assess the atrial effective refractory period and inducibility of AF. Atrial ionic remodeling was measured using the whole-cell patch-clamp technique, and Western blotting and real-time quantitative polymerase chain reactionwere performed to evaluate changes in ion channels. Results CIH induced obvious collagen deposition, and the abnormal fibrosis was significantly attenuated by aliskiren. The inducibility of AF was increased significantly in the CIH group compared with the control and CIH-A groups (23±24.5% vs 2.0±4.2% vs 5.0±7.0%, respectively; P <0.05). Compared with the control group, the densites of the calcium current ( I CaL ) and sodium current ( I Na ) were reduced significantly in the CIH group ( I CaL : −3.16±0.61 pA/pF vs −7.13±1.98 pA/pF; I Na : −50.97±8.71 pA/pF vs −132.58±25.34 pA/pF, respectively; all P <0.05). Following intervention with aliskiren, the reductions in I CaL and I Na were significantly improved, and the ionic modeling changes assessed at the mRNA and protein levels were also significantly improved. Conclusion CIH could alter atrial modeling and subsequently promote the occurrence and development of AF, which could be attenuated by treatment with aliskiren.

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Section: Discussionmentioning

confidence: 93%

<p>The Potential Effects of Aliskiren on Atrial Remodeling Induced by Chronic Intermittent Hypoxia in Rats</p>

Song¹,

Yu²,

Li³

et al. 2020

DDDT

Self Cite

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“…Total protein was extracted by RIPA lysis buffer (KeyGEN Biotech, Nanjing) and then underwent Western blot analysis, as described elsewhere [18]. b-actin served as the loading control.…”

Section: Western Blottingmentioning

confidence: 99%

Doxycycline Improves Fibrosis-Induced Abnormalities in Atrial Conduction and Vulnerability to Atrial Fibrillation in Chronic Intermittent Hypoxia Rats

Zhang

Wang

et al. 2020

Med Sci Monit

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Background: The structural remodeling of atrial architecture, especially increased amounts of fibrosis, is a critical substrate to atrial fibrillation (AF). Doxycycline (Doxy) has recently been shown to exert protective effects against fibrogenic response. This study investigated whether doxycycline (Doxy) can sufficiently ameliorate the fibrosis-induced changes of atrial conduction and AF vulnerability in a chronic intermittent hypoxia (CIH) rat model. Material/Methods: Sixty rats were randomized into 3 groups: Control, CIH, and CIH with Doxy treatment (DOXY) group. CIH rats were exposed to CIH (6 h/d) and Doxy-treated rats were treated with Doxy during processing CIH. After 6 weeks, echocardiographic and hemodynamic parameters were measured. Isolated atrial epicardial activation mapping and heart electrophysiology were performed. The extent of atrial interstitial fibrosis were estimated by Masson's trichrome staining. The expression levels of TGF-b1 and downstream factors were determined by real-Time PCR, immunohistochemistry, and Western blot analysis. Results: Compared to Control rats, the CIH rats showed significant atrial interstitial fibrosis, longer inter-atrial conduction time, and elevated conduction inhomogeneity and AF inducibility, and the expression of TGF-b1, TGF-bRI, TGF-bRII, P-Smad2/3, a-SMA, CTGF, and Collagen I were significantly increased, whereas the velocity of atrial conduction and the expression of miR-30c were dramatically decreased. All of these changes were significantly improved by Doxy treatment. Conclusions: The findings suggested that Doxy can profoundly mitigate atrial fibrosis, conduction inhomogeneity as well as high AF inducibility secondary to fibrosis in a CIH rat model through suppressing the TGF-b1 signaling pathway.

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“…We then examined the effects of BO treatment on the level of Akt phosphorylation at serine 473 (Fig. 4 G), since decreased Akt phosphorylation is involved in the pathogenesis of atrial remodeling and oxidative stress in the atrium, leading to AF 41 , 42 . Akt phosphorylation (Ser-473) was significantly decreased in the atrium of the BO group (Control ( n = 6) vs. BO (n = 7): 1.0 ± 0.1 vs. 0.7 ± 0.1 A.U., P < 0.01 vs. Control).…”

Section: Resultsmentioning

confidence: 99%

“…We then examined the effects of BO treatment on the level of Akt phosphorylation at serine 473 ( Fig. 4G), since decreased Akt phosphorylation is involved in the pathogenesis of atrial remodeling and oxidative stress in the atrium, leading to AF 41,42 . Akt phosphorylation (Ser-473) Supplementary Fig.…”

Section: Effects Of Bo On Akt Phosphorylationmentioning

confidence: 99%

Effects of occlusal disharmony on susceptibility to atrial fibrillation in mice

Suyama

Yagisawa

Okita

et al. 2020

Sci Rep

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Tooth loss or incorrect positioning causes occlusal disharmony. Furthermore, tooth loss and atrial fibrillation (AF) are both risk factors for ischemic stroke and coronary heart disease. Therefore, we hypothesized that occlusal disharmony-induced stress increases susceptibility to AF, and we designed the present study to test this idea in mice. Bite-opening (BO) was done by cementing a suitable appliance onto the mandibular incisor to cause occlusal disharmony by increasing the vertical height of occlusion by 0.7 mm for a period of 2 weeks. AF susceptibility, evaluated in terms of the duration of AF induced by transesophageal burst pacing, was significantly increased concomitantly with atrial remodeling, including fibrosis, myocyte apoptosis and oxidative DNA damage, in BO mice. The BO-induced atrial remodeling was associated with increased calmodulin kinase II-mediated ryanodine receptor 2 phosphorylation on serine 2814, as well as inhibition of Akt phosphorylation. However, co-treatment with propranolol, a non-selective β-blocker, ameliorated these changes in BO mice. These data suggest that improvement of occlusal disharmony by means of orthodontic treatment might be helpful in the treatment or prevention of AF. Abbreviations AF Atrial fibrillation BO Bite-opening β-AR Beta-adrenergic receptor AC Adenylyl cyclase ATP Adenosine triphosphate cAMP Cyclic adenosine monophosphate Epac Exchange protein activated by cAMP Control Control group Pro + BO BO plus propranolol treatment group NS Not significant BW Body weight ECG Electrocardiogram NE Norepinephrine TUNEL Terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-deoxyuridine triphosphate (dUTP) nick-end labeling 8-OHdG 8-Hydroxy-2′-deoxyguanosine CaMKII Calmodulin-dependent protein kinase II Ca 2+ Calcium oxidized-CaMKII Ox-CaMKII RyR2 Ryanodine receptor 2

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Beneficial effects of tolvaptan on atrial remodeling induced by chronic intermittent hypoxia in rats

Abstract: CIH-induced significant atrial remodeling in our rat model, which was attenuated by tolvaptan. These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-κB pathways by tolvaptan.

Cited by 21 publications

References 27 publications

<p>The Potential Effects of Aliskiren on Atrial Remodeling Induced by Chronic Intermittent Hypoxia in Rats</p>

<p>The Potential Effects of Aliskiren on Atrial Remodeling Induced by Chronic Intermittent Hypoxia in Rats</p>

Doxycycline Improves Fibrosis-Induced Abnormalities in Atrial Conduction and Vulnerability to Atrial Fibrillation in Chronic Intermittent Hypoxia Rats

Effects of occlusal disharmony on susceptibility to atrial fibrillation in mice

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