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

Tomomi Nagayama, Yoshitaka Hirooka, Takuya Kishi, Yasushi Mukai, Shuujirou Inoue, Susumu Takase, Masao Takemoto, Akiko Chishaki, Kenji Sunagawa

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

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Angiotensin Type 1 Receptor
Atrial Fibrillation
Brain
Intraventricular Infusions
Blood Pressure
Hypertension
Hydralazine
Losartan
Inbred WKY Rats
Inbred SHR Rats
Renin-Angiotensin System
Oral Administration
Norepinephrine
Fibrosis
Stroke
Maintenance

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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Blockade of brain angiotensin II type 1 receptor inhibits the development of atrial fibrillation in hypertensive rats. / Nagayama, Tomomi; Hirooka, Yoshitaka; Kishi, Takuya; Mukai, Yasushi; Inoue, Shuujirou; Takase, Susumu; Takemoto, Masao; Chishaki, Akiko; Sunagawa, Kenji.

In: American Journal of Hypertension, Vol. 28, No. 4, 01.04.2015, p. 444-451.

Research output: Contribution to journalArticle

Nagayama, T, Hirooka, Y, Kishi, T, 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, vol. 28, no. 4, pp. 444-451. https://doi.org/10.1093/ajh/hpu196
Nagayama, Tomomi ; Hirooka, Yoshitaka ; Kishi, Takuya ; Mukai, Yasushi ; Inoue, Shuujirou ; Takase, Susumu ; Takemoto, Masao ; Chishaki, Akiko ; Sunagawa, Kenji. / Blockade of brain angiotensin II type 1 receptor inhibits the development of atrial fibrillation in hypertensive rats. In: American Journal of Hypertension. 2015 ; Vol. 28, No. 4. pp. 444-451.
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AU - Nagayama, Tomomi

AU - Hirooka, Yoshitaka

AU - Kishi, Takuya

AU - Mukai, Yasushi

AU - Inoue, Shuujirou

AU - Takase, Susumu

AU - Takemoto, Masao

AU - Chishaki, Akiko

AU - Sunagawa, Kenji

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N2 - 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.

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

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