PMID- 25352232
OWN - NLM
STAT- MEDLINE
DCOM- 20151204
LR  - 20150311
IS  - 1941-7225 (Electronic)
IS  - 0895-7061 (Linking)
VI  - 28
IP  - 4
DP  - 2015 Apr
TI  - Blockade of brain angiotensin II type 1 receptor inhibits the development of 
      atrial fibrillation in hypertensive rats.
PG  - 444-51
LID - 10.1093/ajh/hpu196 [doi]
AB  - 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.
CI  - (c) American Journal of Hypertension, Ltd 2014. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Nagayama, Tomomi
AU  - Nagayama T
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate School of 
      Medical Sciences, Fukuoka, Japan;
FAU - Hirooka, Yoshitaka
AU  - Hirooka Y
AD  - Department of Advanced Cardiovascular Regulation and Therapeutics, Kyushu 
      University Graduate School of Medical Sciences, Fukuoka, Japan; 
      hyoshi@cardiol.med.kyushu-u.ac.jp.
FAU - Kishi, Takuya
AU  - Kishi T
AD  - Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu 
      University Graduate School of Medical Sciences, Fukuoka, Japan;
FAU - Mukai, Yasushi
AU  - Mukai Y
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate School of 
      Medical Sciences, Fukuoka, Japan;
FAU - Inoue, Shujiro
AU  - Inoue S
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate School of 
      Medical Sciences, Fukuoka, Japan;
FAU - Takase, Susumu
AU  - Takase S
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate School of 
      Medical Sciences, Fukuoka, Japan;
FAU - Takemoto, Masao
AU  - Takemoto M
AD  - Munakata Suikokai General Hospital, Fukuoka, Japan;
FAU - Chishaki, Akiko
AU  - Chishaki A
AD  - Department of Health Sciences, Kyushu University Graduate School of Medical 
      Sciences, Fukuoka, Japan.
FAU - Sunagawa, Kenji
AU  - Sunagawa K
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate School of 
      Medical Sciences, Fukuoka, Japan;
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141028
PL  - United States
TA  - Am J Hypertens
JT  - American journal of hypertension
JID - 8803676
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 26NAK24LS8 (Hydralazine)
RN  - JMS50MPO89 (Losartan)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/administration & dosage/*pharmacology
MH  - Animals
MH  - Anti-Arrhythmia Agents/administration & dosage/*pharmacology
MH  - Antihypertensive Agents/administration & dosage/*pharmacology
MH  - Atrial Fibrillation/etiology/metabolism/physiopathology/*prevention & control
MH  - Biomarkers/urine
MH  - Blood Pressure/drug effects
MH  - Brain/*drug effects/metabolism/physiopathology
MH  - Disease Models, Animal
MH  - Echocardiography
MH  - Electrocardiography
MH  - Hydralazine/pharmacology
MH  - Hypertension/complications/*drug therapy/metabolism/physiopathology
MH  - Infusions, Intraventricular
MH  - Losartan/administration & dosage/*pharmacology
MH  - Male
MH  - Norepinephrine/urine
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Receptor, Angiotensin, Type 1/*drug effects/metabolism
MH  - Sympathetic Nervous System/drug effects/metabolism/physiopathology
MH  - Time Factors
OTO - NOTNLM
OT  - atrial fibrillation
OT  - blood pressure
OT  - brain angiotensin type 1 receptor
OT  - hypertension
OT  - sympathetic nervous system.
EDAT- 2014/10/30 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/10/30 06:00
PHST- 2014/10/30 06:00 [entrez]
PHST- 2014/10/30 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - hpu196 [pii]
AID - 10.1093/ajh/hpu196 [doi]
PST - ppublish
SO  - Am J Hypertens. 2015 Apr;28(4):444-51. doi: 10.1093/ajh/hpu196. Epub 2014 Oct 28.