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Simultaneous Isolation of High Quality Cardiomyocytes, Endothelial Cells, and Fibroblasts from an Adult Rat Heart
Published on: May 19, 2017
ARB and cardioprotection
Hiroshi Akazawa1, Chizuru Yabumoto, Masamichi Yano
1Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Cardiovascular Drugs and Therapy
|April 28, 2012
Summary
Angiotensin II receptor blockers (ARBs) reduce heart failure risks. Inverse agonist activity, not just blocking Ang II, is key to ARBs' cardioprotective effects by inhibiting receptor activation.
Area of Science:
- Cardiovascular Pharmacology
- Molecular Cardiology
Background:
- Angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are used for congestive heart failure.
- The AT1 receptor, a G protein-coupled receptor, regulates cardiovascular function.
- AT1 receptor exhibits Ang II-independent activity and is activated by mechanical stress.
Purpose of the Study:
- To investigate the role of Ang II-independent AT1 receptor activation in cardiac remodeling.
- To determine the pharmacological mechanisms underlying the cardioprotective effects of ARBs.
Main Methods:
- In vitro studies on AT1 receptor flexibility and spontaneous activity.
- In vivo experimental models of cardiac remodeling.
- Pharmacological evaluation of inverse agonists versus neutral antagonists on AT1 receptor activity.
Main Results:
- AT1 receptor shows Ang II-independent spontaneous activity and activation by mechanical stress.
- Ang II-independent AT1 receptor activation contributes to cardiac remodeling.
- Inverse agonists, but not neutral antagonists, inhibit agonist-independent AT1 receptor activity.
Conclusions:
- Inverse agonist activity is a critical pharmacological parameter for ARBs.
- ARBs exert cardioprotective effects by inhibiting both Ang II-dependent and -independent AT1 receptor activation.
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