Angiotensin II type 1 receptor-mediated reduction of angiotensin-converting enzyme 2 activity in the brain impairs baroreflex function in hypertensive mice.

Hypertension
Huijing XiaEric Lazartigues

Abstract

Angiotensin-converting enzyme 2 (ACE2), a new component of the brain renin-angiotensin system, has been suggested to participate in the central regulation of blood pressure (BP). To clarify the relationship between ACE2 and other brain renin-angiotensin system components, we hypothesized that central angiotensin II type 1 receptors reduce ACE2 expression/activity in hypertensive mice, thereby impairing baroreflex function and promoting hypertension. To test this hypothesis, chronically hypertensive mice (RA) with elevated angiotensin II levels were treated with losartan (angiotensin II type 1 receptor blocker) or PD123319 (angiotensin II type 2 antagonist; 10 mg/kg per day, SC) for 2 weeks. Baseline spontaneous baroreflex sensitivity and brain ACE2 activity were dramatically decreased in RA compared with nontransgenic mice, whereas peripheral ACE2 activity/expression remained unaffected. Losartan, but not PD123319, increased central ACE2 activity, spontaneous baroreflex sensitivity, and normalized BP in RA mice. To confirm the critical role of central ACE2 in BP regulation, we generated a triple-transgenic model with brain ACE2 overexpression on a hypertensive RA background. Triple-transgenic-model mice exhibit lower BP and blu...Continue Reading

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Citations

Apr 29, 2010·Current Hypertension Reports·Huijing Xia, Eric Lazartigues
Apr 3, 2012·Antioxidants & Redox Signaling·Kaushik P Patel, Harold D Schultz
Sep 29, 2011·Cardiovascular Research·Srinivas SriramulaJoseph Francis
Oct 4, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Hong ZhengKaushik P Patel
Dec 24, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Ping XuEric Lazartigues
Sep 2, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Kim Brint PedersenEric Lazartigues
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Jul 31, 2013·IUBMB Life·Kavaljit H ChhabraEric Lazartigues
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Sep 4, 2020·Biological & Pharmaceutical Bulletin·Atsuki HosodaTakeyuki Kohno

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