title: Blockade of brain angiotensin II type 1 receptor inhibits the development of atrial fibrillation in hypertensive rats.
abstract: BACKGROUND
  Hypertension is a powerful risk factor of atrial fibrillation (AF). The pathophysiology of AF with hypertension is associated with sympathoexcitation or the renin-angiotensin system; however, current therapies cannot sufficiently prevent its development. We previously revealed that brain angiotensin II type 1 receptor (AT1R) blockade causes a depressor response via sympathoinhibition. Herein, we evaluated whether brain AT1R contributes to AF development in hypertensive rats.
  
  
  METHODS
  We divided the stroke-prone spontaneously hypertensive rats (SHRSP) treated with intracerebroventricular (ICV) infusion of vehicle, ICV infusion of losartan (S-LOS), or oral administration of hydralazine (S-HYD); and Wistar Kyoto rats treated with ICV S-VEH.
  
  
  RESULTS
  Two weeks later, systolic blood pressure was significantly lower in the S-LOS group than in the S-VEH group and was even lower in the S-HYD group. Urinary norepinephrine excretion for 24h, an indirect marker of sympathoexcitation, significantly reduced in the S-LOS group but increased in the S-HYD group despite depressor response. AF was induced by transesophageal burst pacing. AF duration was significantly shorter in the S-LOS group than in the S-VEH group (5.0±0.4 vs. 15.2±3.7 s; n = 8 each; P < 0.05). However, it was significantly longer in the S-HYD group than in the S-VEH group. Interstitial atrial fibrosis and echocardiographic parameters did not differ between the SHRSP groups.
  
  
  CONCLUSIONS
  Brain AT1R blockade suppresses AF inducibility and maintenance independent of depressor response in hypertensive rats.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nagayama
authors.affiliation: Department of Advanced Cardiovascular Regulation and Therapeutics, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; hyoshi@cardiol.med.kyushu-u.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.affiliation: Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mukai
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Shujiro
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Susumu
authors.initials: S
authors.lastname: Takase
authors.affiliation: Munakata Suikokai General Hospital, Fukuoka, Japan;
authors.forename: Masao
authors.initials: M
authors.lastname: Takemoto
authors.affiliation: Department of Health Sciences, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Chishaki
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004452:Echocardiography; D004562:Electrocardiography; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D057967:Infusions, Intraventricular; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000652:urine; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D006830:Hydralazine; D019808:Losartan; D009638:Norepinephrine
keywords: atrial fibrillation; blood pressure; brain angiotensin type 1 receptor; hypertension; sympathetic nervous system.