Angiotensin i to angiotensin ii
Pro Research Analysisby 
Searched over 200M research papers
Conversion of Angiotensin I to Angiotensin II: Mechanisms and Implications
Angiotensin-Converting Enzyme (ACE) and Its Role
The conversion of angiotensin I to angiotensin II is primarily facilitated by the angiotensin-converting enzyme (ACE). This enzyme not only converts angiotensin I to the potent vasoconstrictor angiotensin II but also inactivates bradykinin, a peptide that promotes vasodilation. ACE is found in various tissues, including the vascular endothelial cells of the lungs and peripheral blood vessels, as well as the epithelial cells of the kidney tubules . The inhibition of ACE can block the renin-angiotensin system (RAS), leading to decreased systemic blood pressure, especially in conditions where blood pressure is maintained or increased by renin .
Angiotensin II and Cardiovascular Diseases
Angiotensin II (Ang II) is a critical bioactive peptide within the RAS, playing a significant role in the development of cardiovascular diseases (CVD). Ang II exerts its effects primarily through the angiotensin type 1 receptor (AT1R), leading to vasoconstriction, increased blood pressure, and other deleterious cardiovascular effects . Pharmacological inhibition of ACE or blockade of Ang II binding to AT1R has been shown to provide protection against the progression of CVD .
Noncanonical Pathways and Intracrine Functions
Recent research has highlighted the existence of noncanonical pathways for Ang II formation, particularly within the human heart. One such pathway involves the dodecapeptide angiotensin-(1-12) [Ang-(1-12)], which can generate Ang II directly via chymase, bypassing the traditional ACE pathway. This alternative pathway may be crucial in understanding the mechanisms by which Ang II contributes to adverse cardiac and vascular remodeling .
Predominance of ACE Pathway in the Human Heart
Despite the presence of non-ACE pathways, studies have shown that the ACE pathway remains the predominant route for Ang II formation in the human heart. In vivo experiments involving intracoronary administration of labeled angiotensin I and the ACE inhibitor enalaprilat demonstrated that ACE is responsible for the majority of Ang II production in myocardial tissue . This finding underscores the importance of ACE in the regulation of Ang II levels within the heart.
Protective Role of ACE2 and Angiotensin (1-7)
The ACE homologue, ACE2, plays a counter-regulatory role by converting Ang II to angiotensin (1-7) [Ang (1-7)], a peptide with vasodilatory and cardioprotective effects. The ACE2-Ang (1-7) axis has been shown to counterbalance the harmful effects of the ACE-Ang II-AT1R axis. Elevated expression of ACE2 and Ang (1-7) in failing heart tissue suggests a protective role, potentially offering therapeutic benefits in cardiovascular conditions .
Conclusion
The conversion of angiotensin I to angiotensin II is a critical process mediated predominantly by ACE, with significant implications for cardiovascular health. While noncanonical pathways and intracrine functions of Ang II add complexity to this system, the ACE pathway remains the primary route for Ang II formation in the heart. Understanding these mechanisms provides valuable insights into potential therapeutic strategies for managing cardiovascular diseases.
Sources and full results
Most relevant research papers on this topic
An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update
Angiotensin II signaling in the cardiovascular system has evolved significantly, with recent discoveries potentially guiding therapeutic strategies and stem cell-based therapies.
Angiotensin II formation in the intact human heart. Predominance of the angiotensin-converting enzyme pathway.
The predominant pathway for angiotensin II formation in the human heart is through angiotensin-converting enzyme (ACE).
Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.
The angiotensin II type 1 receptor (AT1R) plays a central role in cardiovascular physiology and pathophysiology, with potential therapeutic applications in treating various diseases.
Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases.
Angiotensin II plays a central role in the pathophysiology of cardiovascular and renal diseases, affecting cell growth, gene expression, and intracellular signaling cascades.
Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart.
The major angiotensin II-forming enzyme in the human heart is a novel chymase with high specificity for converting angiotensin I to Ang II and the dipeptide His-Leu.
Pathways of angiotensin-(1-7) metabolism in the kidney.
Novel pathways in the kidney reveal potential actions of angiotensin-(1-7) and potential novel vasoactive peptidase therapies.
DOI