Blockade of brain angiotensin II type 1 receptor inhibits the development of atrial fibrillation in hypertensive rats

Tomomi Nagayama, Yoshitaka Hirooka, Y. Kishi, Yasushi Mukai, Shujiro Inoue, Susumu Takase, Masao Takemoto, Akiko Chishaki, Kenji Sunagawa

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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. CONCLUSIONSL: Brain AT1R blockade suppresses AF inducibility and maintenance independent of depressor response in hypertensive rats.

Original languageEnglish
Pages (from-to)444-451
Number of pages8
JournalAmerican Journal of Hypertension
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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    Nagayama, T., Hirooka, Y., Kishi, Y., Mukai, Y., Inoue, S., Takase, S., Takemoto, M., Chishaki, A., & Sunagawa, K. (2015). Blockade of brain angiotensin II type 1 receptor inhibits the development of atrial fibrillation in hypertensive rats. American Journal of Hypertension, 28(4), 444-451. https://doi.org/10.1093/ajh/hpu196