Angiotensinogen 2 function
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Functions of Angiotensin II Type 2 Receptor (AT2-R)
Introduction to Angiotensin II and Its Receptors
Angiotensin II (Ang II) is a critical peptide in the renin-angiotensin system (RAS), which regulates blood pressure, fluid balance, and cardiovascular functions. Ang II exerts its effects through two main receptor subtypes: Ang II type 1 receptor (AT1-R) and Ang II type 2 receptor (AT2-R) .
AT2-R Expression and Regulation
AT2-R is highly expressed in fetal tissues but has low expression in adult tissues under normal conditions. However, its expression can increase significantly in response to pathological states such as tissue injury, inflammation, and cardiovascular diseases . This receptor is re-expressed in adult tissues during conditions like heart failure and vascular injury, where it plays a role in modulating tissue remodeling and inflammation.
Counter-Regulatory Role of AT2-R
AT2-R often acts in opposition to AT1-R. While AT1-R mediates vasoconstriction, cell proliferation, and sodium retention, AT2-R promotes vasodilation, inhibits cell proliferation, and enhances natriuresis (excretion of sodium in urine) . This counter-regulatory function is crucial in maintaining cardiovascular and renal homeostasis, especially under pathological conditions .
Mechanisms of Action
Vasodilation and Blood Pressure Regulation
AT2-R induces vasodilation primarily through the activation of the bradykinin/nitric oxide (NO)/cyclic GMP (cGMP) pathway. This pathway involves the production of bradykinin, which stimulates NO release, leading to increased cGMP levels and subsequent vasodilation . This mechanism helps counteract the vasoconstrictive effects mediated by AT1-R, thereby contributing to blood pressure regulation .
Inhibition of Cell Proliferation and Promotion of Apoptosis
AT2-R inhibits cell proliferation and promotes apoptosis, which is the programmed death of cells. This is achieved through the dephosphorylation of proteins, counteracting the phosphorylation effects mediated by AT1-R . This function is particularly important in preventing excessive tissue growth and fibrosis during pathological conditions .
Role in Tissue Remodeling
In conditions like heart failure and vascular injury, AT2-R is re-expressed and helps attenuate tissue remodeling by inhibiting Ang II-induced mitogenic signals and the synthesis of extracellular matrix proteins. This action helps reduce fibrosis and improve tissue function .
Clinical Implications
The beneficial effects of AT2-R in cardiovascular and renal diseases have significant clinical implications. Selective stimulation of AT2-R, especially in the presence of AT1-R antagonists, can enhance its protective effects, offering potential therapeutic strategies for conditions like hypertension, heart failure, and kidney diseases .
Conclusion
Angiotensin II type 2 receptor (AT2-R) plays a crucial counter-regulatory role in the renin-angiotensin system. It promotes vasodilation, inhibits cell proliferation, and aids in tissue remodeling, opposing the effects of AT1-R. Understanding the functions and mechanisms of AT2-R can lead to better therapeutic strategies for managing cardiovascular and renal diseases.
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