title: Telmisartan reduces atrial arrhythmia susceptibility through the regulation of RAS-ERK and PI3K-Akt-eNOS pathways in spontaneously hypertensive rats.
abstract: Telmisartan is an angiotensin II receptor blocker that displays unique PPAR-γ modulating activity. PPAR-γ agonists have been shown to decrease susceptibility to atrial fibrillation through their antioxidant and antiapoptotic effects. The aim of this study was to determine whether telmisartan would have a greater effect on susceptibility to atrial arrhythmia in a hypertensive rat model than valsartan, which is a traditional angiotensin II receptor blocker. In this study, spontaneously hypertensive rats were treated with 10 mg·(kg body mass)(-1)·d(-1) telmisartan (TEL group), 10 mg·(kg body mass)(-1)·d(-1) valsartan (VAL group), or vehicle (saline; SHR group) for 4 weeks. Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. After 4 weeks of treatment, we performed echocardiographic assessment, electrophysiological analysis, histological evaluation, and Western blot analysis. Telmisartan decreased systolic blood pressure to a similar extent as valsartan. Relative to the WKY controls, atrial arrhythmia susceptibility was significantly increased in the SHR group, and was significantly decreased by both telmisartan and valsartan, albeit to a greater extent with telmisartan. Arrhythmogenic atrial remodeling, including enlargement of the left atrium, myocyte hypertrophy, interstitial fibrosis, and myocyte apoptosis, was observed in the SHR group, and was accompanied by activated RAS-ERK signaling and suppressed PI3K-Akt-eNOS signaling. The results suggest that telmisartan reduced susceptibility to atrial arrhythmia to a greater extent than valsartan, ameliorated atrial remodeling, and reversed imbalances in the RAS-ERK and PI3K-Akt-eNOS pathways.
authors.affiliation: Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.|Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Wang
authors.affiliation: Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.|Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.
authors.forename: Fei-Long
authors.initials: FL
authors.lastname: Zhang
authors.affiliation: Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.|Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.|Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.
authors.forename: Xue-Hai
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.|Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.
authors.forename: Fa-Yuan
authors.initials: FY
authors.lastname: Fu
authors.affiliation: Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.|Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.
authors.forename: Mi-Rong
authors.initials: MR
authors.lastname: Tang
authors.affiliation: Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.|Department of Coronary Artery Disease, Union Hospital, Union Clinic Medical College, Fujian Medical University, 29 Xin-Quan Road, Fuzhou 350001, China.
authors.forename: Liang-Long
authors.initials: LL
authors.lastname: Chen
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001145:Arrhythmias, Cardiac / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D064752:Atrial Remodeling / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005355:Fibrosis; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects; D000077333:Telmisartan; D013997:Time Factors; D000068756:Valsartan / Q000494:pharmacology; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D000068756:Valsartan; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins; D000077333:Telmisartan
keywords: angiotensin receptor blockers; antagonistes du récepteur de l’angiotensine; atrial fibrillation; fibrillation auriculaire; hypertension; remodelage structural; signaling pathway; structural remodeling; voie de signalisation