Renin-Angiotensin System Modulation in Vascular Disease

The renin-angiotensin system (RAS) constitutes a pivotal hormonal cascade that regulates vascular tone, fluid balance and inflammatory responses. In its classical pathway, renin cleaves angiotensinogen to yield angiotensin I, which is converted by angiotensin-converting enzyme (ACE) to angiotensin II. This octapeptide engages the angiotensin II type 1 receptor (AT₁R) to induce vasoconstriction, sodium retention and pro-inflammatory signalling. Beyond its circulatory actions, tissue-specific RAS components reside in the vascular wall, heart and kidney, where local synthesis of angiotensin II promotes oxidative stress, endothelial dysfunction and vascular remodelling. Pharmacological blockade of RAS with ACE inhibitors, angiotensin II receptor blockers (ARBs) or direct renin inhibitors (DRIs) has been firmly established in the management of hypertension, heart failure, diabetic vasculopathy and atherosclerosis. More recent advances have addressed the balance between angiotensin II and protective peptides such as angiotensin-(1-7), which acts via the Mas receptor to induce vasodilatation and anti-inflammatory effects. Efforts to refine RAS modulation include selective AT₂R agonists, biased AT₁R ligands, ACE2 activators and tissue-targeted delivery systems. Although dual RAS inhibition was once considered for enhanced benefit, large clinical trials demonstrated increased adverse events without mortality reduction, reinforcing single-pathway blockade as the mainstay. Emerging research is now focusing on cell-specific RAS modulation, interplay with immune cells and integration with lipid-lowering and antioxidant therapies to limit vascular injury and promote repair. This broad body of work underscores the global importance of RAS modulation for cardiovascular risk reduction and highlights practical applications ranging from blood-pressure control to mitigation of plaque inflammation and vascular stiffening.

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Renin-Angiotensin System Modulation in Vascular Disease publication trend

The graph below shows the total number of articles in renin-angiotensin system modulation in vascular disease across all publications each year (not limited to Nature Index journals).

Technical terms

Renin: Enzyme secreted by the kidney that initiates the RAS cascade by cleaving angiotensinogen.

Angiotensin II: Peptide hormone that binds AT₁R to induce vasoconstriction, sodium retention and inflammatory signalling.

ACE inhibitors: Drugs that block angiotensin-converting enzyme, reducing production of angiotensin II and enhancing bradykinin levels.

ARBs: Angiotensin II receptor blockers that selectively inhibit AT₁R, preventing downstream vasoconstrictive and pro-inflammatory effects.

Vascular smooth muscle cell (VSMC): Principal cell type in the arterial media that regulates vessel tone and contributes to atherosclerotic remodelling.

References

1. Dual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials challenge existing evidence?. Cardiovascular Diabetology (2013).
2. Angiotensin II, Hypercholesterolemia, and Vascular Smooth Muscle Cells: A Perfect Trio for Vascular Pathology. International Journal of Molecular Sciences (2020).
3. Renin angiotensin system blockage by losartan neutralize hypercholesterolemia-induced inflammatory and oxidative injuries. Redox Report (2020).
4. Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis. PLOS ONE (2019).