Renin-Angiotensin-Aldosterone System in Cardiac Health

The renin–angiotensin–aldosterone system (RAAS) is a hierarchical endocrine cascade that governs arterial pressure, vascular tone and sodium–water balance, thereby exerting profound influence on cardiac structure and function. Initiated by renin release from juxtaglomerular cells, angiotensin I is converted to angiotensin II, a potent vasoconstrictor that stimulates aldosterone secretion and promotes maladaptive myocardial hypertrophy and fibrosis when chronically activated. While acute RAAS activation supports perfusion in low-output states, sustained engagement contributes to adverse cardiac remodelling, progression of heart failure and arrhythmogenesis. Therapeutic blockade of classical RAAS mediators via angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or mineralocorticoid receptor antagonists has become standard care in systolic dysfunction, yet individual response varies due to genetic polymorphisms, breakthrough aldosterone production and alternative pathway modulation. Contemporary research seeks to elucidate biomarkers for precise pathway assessment, to refine dosing strategies and to explore dual modulation of classical and counter-regulatory axes in order to optimise long-term cardiac outcomes globally.

Research from Nature Portfolio

Recent studies in large-animal models have characterised dose-dependent effects of an angiotensin-converting enzyme inhibitor on both classical and alternative RAAS pathways. Time-resolved measurements of plasma renin activity, angiotensin I and II, and surrogate indices of ACE and alternative pathway activity revealed that escalating doses yielded progressive suppression of angiotensin II and downstream metabolites, accompanied by compensatory rises in angiotensin I and renin activity. Notably, hemodynamic parameters remained stable across dosing regimens, underscoring the potential for tailored biomarker-guided optimisation of inhibitor dosing in translational and clinical trials.

Renin-Angiotensin-Aldosterone System in Cardiac Health publication trend

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

Technical terms

Renin: A proteolytic enzyme released from the kidney that catalyses the conversion of angiotensinogen to angiotensin I.

Angiotensin II: A bioactive peptide that induces vasoconstriction, aldosterone secretion and myocardial hypertrophy.

Aldosterone: A mineralocorticoid hormone that promotes sodium retention, potassium excretion and contributes to fibrosis when chronically elevated.

ACE inhibitor: A drug class that prevents the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone release.

Aldosterone breakthrough: Resumption of aldosterone synthesis despite ongoing RAAS inhibition, potentially driven by non-angiotensin pathways.

Cardiac remodelling: Structural and functional alterations in the myocardium in response to injury or haemodynamic stress.

References

1. Dose–response of benazepril on biomarkers of the classical and alternative pathways of the renin–angiotensin–aldosterone system in dogs. Scientific Reports (2023).
2. Changes in renin‐angiotensin‐aldosterone system during cardiac remodeling after mitral valvuloplasty in dogs. Journal of Veterinary Internal Medicine (2022).
3. Factors affecting the urinary aldosterone-to-creatinine ratio in healthy dogs and dogs with naturally occurring myxomatous mitral valve disease. BMC Veterinary Research (2021).
4. Impact of Renin-Angiotensin-Aldosterone System Gene Polymorphisms on Left Ventricular Dysfunction in Coronary Artery Disease Patients. Disease Markers (2012).