Tomomi Nagayama 1 , Yoshitaka Hirooka 2 , Takuya Kishi 3 , Yasushi Mukai 1 , Shujiro Inoue 1 , Susumu Takase 1 , Masao Takemoto 4 , Akiko Chishaki 5 , Kenji Sunagawa 1 Show Affiliations »
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. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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 . © American Journal of Hypertension , Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Species
Keywords:
atrial fibrillation; blood pressure; brain angiotensin type 1 receptor; hypertension; sympathetic nervous system.
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Year: 2014
PMID： 25352232 DOI： 10.1093/ajh/hpu196
Source DB: PubMed Journal: Am J Hypertens ISSN： 0895-7061 Impact factor: 2.689