Rapid Communication - Journal of Cancer Clinical Research (2025) Volume 8, Issue 1

Key Functions of the Angiotensin II Pathway in Cardiovascular Regulation and Disorders

Article type: Rapid Communication

Home Page URL:  https://www.alliedacademies.org/journal-cancer-clinical-research/

Journal short name: J Can Clinical Res

Volume: 8

Issue: 1

PDF No: 183

Citation: Mehran R. Key Functions of the Angiotensin II Pathway in Cardiovascular Regulation and Disorders. J Can Clinical Res. 2025; 8(1):183

^*Correspondence to: Roxana Mehran, Director, Center for Interventional Cardiovascular Research and Clinical Trials, Mount Sinai, USA. Email: roxana.mehran@mountsinai.org

Received: 27-May-2025, Manuscript No. AACCR-25-169795; Editor assigned: 01-Jun-2025, PreQC No. AACCR-25-169795 (PQ); Reviewed: 15- Jun-2025, QC No. AACCR-25-169795; Revised: 22- Jun-2025, Manuscript No. AACCR-25-169795 (R); Published: 29- Jun-2025, DOI:10.35841/AATCC-8.1.183

Key Functions of the Angiotensin II Pathway in Cardiovascular Regulation and Disorders

Roxana Mehran*

Director, Center for Interventional Cardiovascular Research and Clinical Trials, Mount Sinai, USA

Introduction

Angiotensin II is a key peptide in the renin-angiotensin system (RAS), an essential regulatory mechanism for blood pressure, fluid balance, and electrolyte homeostasis. Generated from angiotensin I through the enzymatic activity of angiotensin-converting enzyme (ACE), angiotensin II exerts profound effects on the cardiovascular system. It acts primarily through the angiotensin II type 1 receptor (AT1R), initiating vasoconstriction, sodium retention, aldosterone secretion, and sympathetic activation. These actions serve to maintain circulatory stability during physiological stress but, when chronically activated, contribute to pathological states such as hypertension, heart failure, chronic kidney disease, and atherosclerosis.The angiotensin II pathway involves a cascade of molecular and cellular events that commence with the cleavage of angiotensinogen by renin, forming angiotensin I. Subsequently, angiotensin I is converted into angiotensin II by ACE. Angiotensin II binds predominantly to AT1 receptors distributed widely in vascular smooth muscle cells, myocardium, kidneys, and the central nervous system. Binding to AT1R activates several intracellular signaling pathways including G-protein coupled receptor mechanisms, leading to increased intracellular calcium, activation of protein kinase C, and subsequent activation of pro-inflammatory and pro-fibrotic transcription factors such as nuclear factor-kappa B (NF-κB). These mechanisms underscore its potent vasopressor activity and its ability to induce vascular remodeling, endothelial dysfunction, and organ fibrosis.

At the systemic level, angiotensin II promotes arteriolar vasoconstriction, raising systemic vascular resistance and blood pressure. It also stimulates the adrenal cortex to secrete aldosterone, promoting sodium and water reabsorption in the renal distal tubules, thereby increasing intravascular volume and reinforcing blood pressure elevation. Additionally, it enhances the release of antidiuretic hormone (ADH) from the posterior pituitary, further contributing to water retention. The sympathetic nervous system is also potentiated by angiotensin II, increasing norepinephrine release and decreasing its reuptake, which further amplifies vasoconstriction and cardiac output. It is noteworthy that angiotensin II also acts through the angiotensin II type 2 receptor (AT2R), which mediates counter-regulatory effects including vasodilation, natriuresis, and anti-proliferative actions. The physiological relevance of AT2R remains under investigation, but its activation may represent a protective mechanism against AT1R-mediated damage. The development of selective AT2R agonists is an area of ongoing research, offering a potential new avenue for therapeutic intervention.

Beyond hemodynamic effects, angiotensin II contributes significantly to structural cardiovascular changes. Chronic exposure induces hypertrophy of vascular smooth muscle and cardiac myocytes, leading to increased wall thickness and reduced compliance of blood vessels and the heart. These structural alterations are central to the pathogenesis of hypertension-induced target organ damage. Moreover, angiotensin II induces oxidative stress through activation of NADPH oxidase, generating reactive oxygen species (ROS) that reduce nitric oxide bioavailability and promote endothelial dysfunction. This impairment in endothelial homeostasis accelerates atherogenesis, plaque instability, and thrombogenesis, establishing a link between the angiotensin II pathway and ischemic cardiovascular events such as myocardial infarction and stroke.

Inflammation is another critical dimension of angiotensin II activity. It stimulates the production of pro-inflammatory cytokines, chemokines, and adhesion molecules, recruiting leukocytes to vascular tissues and perpetuating chronic inflammation. This process not only exacerbates vascular damage but also contributes to the progression of heart failure and chronic kidney disease. In the kidney, angiotensin II constricts efferent arterioles, raising glomerular capillary pressure and promoting proteinuria and glomerulosclerosis. These mechanisms underline the significance of the angiotensin II pathway in the pathophysiology of renal diseases.

Therapeutically, the modulation of the angiotensin II pathway has revolutionized the management of cardiovascular and renal diseases. ACE inhibitors, angiotensin receptor blockers (ARBs), and more recently angiotensin receptor-neprilysin inhibitors (ARNIs) have become mainstays in the treatment of hypertension, heart failure, and diabetic nephropathy. These agents attenuate the adverse effects of angiotensin II by inhibiting its formation or blocking its receptor, thereby reducing blood pressure, reversing cardiac remodeling, improving endothelial function, and lowering the incidence of adverse cardiovascular events. Clinical trials such as HOPE, LIFE, and PARADIGM-HF have demonstrated significant morbidity and mortality benefits with agents targeting this pathway, solidifying their central role in evidence-based cardiovascular therapeutics.

Conclusion

The angiotensin II pathway stands at the crossroads of physiological regulation and pathological disruption. Its role in controlling blood pressure, fluid homeostasis, and vascular tone is indispensable to survival, yet its chronic overactivity underlies a multitude of cardiovascular and renal disorders. Therapeutic targeting of this pathway has profoundly improved the management of these diseases, and ongoing research continues to unveil its complex biology. A comprehensive understanding of angiotensin II signaling and its interaction with other regulatory systems will not only enhance therapeutic precision but also foster the development of innovative treatments aimed at restoring vascular and metabolic health.

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