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[Angiotensin II receptor-mediated function unmasked by gene-engineered animals]
1Department of Medicine II, Kansai Medical University.
Nihon Rinsho. Japanese Journal of Clinical Medicine
|June 11, 1999
Summary
The angiotensin II type 2 receptor (AT2-R) plays a protective role in the cardiovascular system, counteracting angiotensin II effects. Its activation promotes vasodilation and cardioprotection, especially in humans.
Area of Science:
- Cardiovascular Physiology
- Receptor Pharmacology
- Molecular Biology
Context:
- Angiotensin II (Ang II) exerts critical cardiovascular effects primarily via the AT1-R.
- AT2-R expression is high in fetal development but low in adult cardiovascular tissues.
- Overexpression of AT2-R in cardiac myocytes or vascular smooth muscle inhibits Ang II actions.
Purpose:
- To elucidate the functional role of the angiotensin II type 2 receptor (AT2-R) in cardiovascular regulation.
- To investigate the signaling pathways and physiological consequences of AT2-R activation.
- To compare AT2-R expression and function between species and in response to therapeutic interventions.
Summary:
- AT2-R activation inhibits Ang II-induced chronotropic and pressor responses, suggesting a role in regulating cardiac pacemaker activity and vascular resistance.
- AT2-R stimulates the kinin/nitric oxide/cGMP pathway, mediating cardioprotection, vasodilation, and pressure natriuresis.
- AT2-R exerts its effects via Gi-protein-dependent activation of protein tyrosine and serine/threonine phosphatases.
- Human hearts exhibit higher AT2-R expression than rodents, implying enhanced AT2-R-mediated effects, particularly with AT1-R antagonist therapy.
Impact:
- AT2-R represents a potential therapeutic target for cardiovascular diseases.
- Understanding AT2-R signaling can lead to novel strategies for managing hypertension and heart failure.
- The enhanced AT2-R activity in humans suggests specific therapeutic potential for this receptor subtype.