Angiotensin 1 and 2
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Understanding Angiotensin 1 and 2: Key Roles in Cardiovascular Regulation
Introduction to Angiotensin 1 and 2
Angiotensin I (Ang I) and Angiotensin II (Ang II) are critical components of the renin-angiotensin system (RAS), which plays a vital role in regulating blood pressure, fluid balance, and systemic vascular resistance. Ang I is a precursor that is converted into the more active Ang II, which exerts significant physiological effects.
Angiotensin-Converting Enzyme 2 (ACE2) and Angiotensin-(1-7)
ACE2 and Its Function
Angiotensin-converting enzyme 2 (ACE2) is a key enzyme that modulates the RAS by converting Ang II into Angiotensin-(1-7). This conversion is crucial because Ang-(1-7) has been found to counteract many of the harmful effects of Ang II, such as vasoconstriction and cell proliferation .
Role of Angiotensin-(1-7)
Angiotensin-(1-7) is now recognized as a biologically active component of the RAS. It exerts a range of actions that are often opposite to those of Ang II, including vasodilation and anti-proliferative effects . The discovery of ACE2 has highlighted an important metabolic pathway responsible for Ang-(1-7) synthesis, which can occur either directly from Ang II or through the hydrolysis of Ang I to Ang-(1-9) and subsequent conversion to Ang-(1-7) by ACE.
Angiotensin II Receptors: AT1 and AT2
AT1 Receptor
The Angiotensin II type 1 receptor (AT1R) is well-studied and is known to mediate most of the classical effects of Ang II, including vasoconstriction, sodium retention, and cell proliferation . These actions contribute to the regulation of blood pressure and fluid balance but can also lead to pathological conditions such as hypertension and organ damage when overactivated.
AT2 Receptor
In contrast, the Angiotensin II type 2 receptor (AT2R) has been less understood but is increasingly recognized for its counter-regulatory roles. The AT2R opposes many of the actions of the AT1R, promoting vasodilation, natriuresis (excretion of sodium in urine), and inhibition of cell proliferation . This receptor is particularly interesting because it is upregulated in pathological conditions and may offer protective effects against cardiovascular and renal diseases .
Interactions and Implications
ACE2/Ang-(1-7)/Mas Axis
The ACE2/Ang-(1-7)/Mas axis represents an endogenous counter-regulatory pathway within the RAS. This axis opposes the vasoconstrictive and proliferative actions of the ACE/Ang II/AT1R pathway, thereby playing a protective role in cardiovascular and renal systems. The G protein-coupled receptor Mas is a functional binding site for Ang-(1-7), further emphasizing the importance of this axis in mitigating the adverse effects of Ang II.
Therapeutic Potential
Understanding the balance between the ACE/Ang II/AT1R and ACE2/Ang-(1-7)/Mas pathways opens new avenues for therapeutic interventions. Targeting the AT2R with specific agonists like C21 has shown promise in treating conditions such as hypertension, obesity, and kidney diseases. Additionally, enhancing the activity of the ACE2/Ang-(1-7)/Mas axis could offer protective benefits against cardiovascular and renal pathologies.
Conclusion
The interplay between Angiotensin I and II, their converting enzymes, and their receptors is complex but crucial for maintaining cardiovascular and renal health. The ACE2/Ang-(1-7)/Mas axis provides a counterbalance to the potentially harmful effects of the ACE/Ang II/AT1R pathway, highlighting the importance of these components in therapeutic strategies for cardiovascular diseases. Understanding these mechanisms further can lead to more effective treatments and improved outcomes for patients with hypertension and related conditions.
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