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: Tomomi Nagayama, Yoshitaka Hirooka, Takuya Kishi, Yasushi Mukai, Shujiro Inoue, Susumu Takase, Masao Takemoto, Akiko Chishaki, Kenji Sunagawa
• Journal: American journal of hypertension (Am J Hypertens) Vol. 28 Issue 4 Pg. 444-51 (Apr 2015) ISSN: 1941-7225 [Electronic] United States
• PMID: 25352232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Anti-Arrhythmia Agents
• Antihypertensive Agents
• Biomarkers
• Receptor, Angiotensin, Type 1
• Hydralazine
• Losartan
• Norepinephrine

Topics

• Angiotensin II Type 1 Receptor Blockers (administration & dosage, pharmacology)
• Animals
• Anti-Arrhythmia Agents (administration & dosage, pharmacology)
• Antihypertensive Agents (administration & dosage, pharmacology)
• Atrial Fibrillation (etiology, metabolism, physiopathology, prevention & control)
• Biomarkers (urine)
• Blood Pressure (drug effects)
• Brain (drug effects, metabolism, physiopathology)
• Disease Models, Animal
• Echocardiography
• Electrocardiography
• Hydralazine (pharmacology)
• Hypertension (complications, drug therapy, metabolism, physiopathology)
• Infusions, Intraventricular
• Losartan (administration & dosage, pharmacology)
• Male
• Norepinephrine (urine)
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptor, Angiotensin, Type 1 (drug effects, metabolism)
• Sympathetic Nervous System (drug effects, metabolism, physiopathology)
• Time Factors