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[Recent progress in AT1 and AT2 receptor research]
1Department of Medical Biochemistry, Ehime University School of Medicine.
Abstract:
AT1 and AT2 receptors seem to be mutually antagonistic and the upregulation of AT2 receptor would play a role in the pathogenesis and remodeling of cardiovascular and renal diseases. AT2 receptor is abundantly and widely expressed in fetal tissues, but present at low levels in adult tissues and re-expressed in certain pathological conditions such as vascular injury. The overall cellular effect of AT2 and AT1 receptors co-stimulation is a premature termination of AT1 receptors-elicited cell growth signals by AT2 receptors. Our recent results using AT2 receptor null mice suggest that selective AT1 receptor blockade as well as the stimulation of uninhibited AT2 receptor by angiotensin II is important in the ARB-mediated improvement of cardiovascular remodeling.
Insights
The AT2 receptor, often downregulated in adults but re-expressed in disease, antagonizes AT1 receptors. Stimulating AT2 receptors aids cardiovascular remodeling, particularly with AT1 receptor blockade.
Area of Science:
- Cardiovascular Physiology
- Renal Physiology
- Molecular Biology
Context:
- The renin-angiotensin system (RAS) plays a critical role in cardiovascular and renal homeostasis.
- Angiotensin II type 1 (AT1) and type 2 (AT2) receptors exhibit antagonistic functions.
- AT2 receptor expression is high in fetal tissues, low in adults, but upregulated during pathological conditions like vascular injury.
Purpose:
- To investigate the role of AT2 receptor in cardiovascular remodeling.
- To elucidate the interplay between AT1 and AT2 receptor signaling.
- To evaluate the therapeutic potential of modulating AT2 receptor activity.
Summary:
- AT1 and AT2 receptors demonstrate mutual antagonism.
- Co-stimulation of AT1 and AT2 receptors leads to premature termination of AT1-mediated cell growth signals by AT2.
- In AT2 receptor null mice, angiotensin II stimulation of the uninhibited AT2 receptor is crucial for Angiotensin Receptor Blocker (ARB)-mediated cardiovascular remodeling improvements.
Impact:
- Selective AT1 receptor blockade combined with AT2 receptor stimulation may offer a novel therapeutic strategy for cardiovascular diseases.
- Understanding AT2 receptor function is vital for developing treatments for cardiovascular and renal pathologies.
- This research highlights the importance of the AT2 receptor in mitigating pathological remodeling processes.