AT2 receptor agonists: hypertension and beyond

Area of Science:

• Pharmacology
• Cardiovascular Research
• Nephrology

Background:

• Research on the angiotensin AT2 receptor (AT2R) was limited by the absence of stable, selective agonists for in-vivo studies.
• The recent availability of compound 21, a specific AT2R agonist, has revitalized research in this field.
• This review focuses on studies utilizing direct AT2R stimulation, excluding receptor blockade or genetic modification approaches.

Purpose of the Study:

• To review recent publications investigating the functional role of the angiotensin AT2 receptor (AT2R) via direct in-vivo stimulation.
• To assess the impact of AT2R activation on various disease models.

Main Methods:

• Review of 14 original publications focusing on AT2R function.
• Analysis of studies employing direct in-vivo stimulation with a specific AT2R agonist (compound 21).
• Examination of disease models including hypertension, renal disease, stroke, Alzheimer's disease, and myocardial infarction.

Main Results:

• AT2R stimulation did not demonstrate antihypertensive effects.
• Significant tissue protection was observed across all tested experimental disease models.
• Anti-inflammatory and anti-apoptotic properties of AT2R appear to contribute to improved outcomes.

Conclusions:

• The development of non-peptidic, orally active AT2R agonists is crucial for advancing AT2R research.
• AT2R agonists hold promise as a novel class of therapeutic agents.
• AT2R agonists are anticipated to enter Phase I clinical trials soon.