Renin-Angiotensin System Dynamics in Cardiovascular and Renal Health

The renin-angiotensin system (RAS) is a hormone network fundamental to the regulation of blood pressure, fluid balance and electrolyte homoeostasis. Initiated by the release of renin from juxtaglomerular cells in response to reduced perfusion pressure or sympathetic stimulation, the cascade generates angiotensin I and its conversion to angiotensin II (Ang II) via angiotensin-converting enzyme (ACE). Ang II exerts vasoconstrictive, pro-inflammatory and pro-fibrotic effects through the angiotensin II type 1 receptor (AT1R), while counter-regulatory pathways—mediated by ACE2, Ang 1-7 and the Mas receptor—promote vasodilation, anti-inflammation and anti-remodelling. Tissue-specific RAS components within the heart and kidney modulate local haemodynamics, sodium transport and cellular growth. Dysregulation of either classical or alternative axes contributes to hypertension, cardiac hypertrophy, renal fibrosis and acute kidney injury. Recent research has deepened our understanding of how modulation of genetic networks, alternative peptidases and biased receptor signalling can reset long-term pressures in experimental models and open new therapeutic avenues for cardiovascular and renal diseases.

Research from Nature Portfolio

A seminal study demonstrated that Ang 1-7 functions as an endogenous β-arrestin-biased agonist at AT1R, uncoupling G protein signalling while recruiting β-arrestins 1 and 2. In an in vivo model of pressure-overload hypertrophy, administration of Ang 1-7 markedly reduced ventricular wall thickness, heart weight and end-diastolic pressure. Combined blockade of AT1R and Mas receptor only partially abrogated these benefits, suggesting a dual-receptor mechanism underpinning cardioprotection via biased agonism.

Renin-Angiotensin System Dynamics in Cardiovascular and Renal Health publication trend

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

Technical terms

Renin: A protease released by kidney juxtaglomerular cells that cleaves angiotensinogen to angiotensin I, initiating the RAS cascade.

Angiotensin II (Ang II): A potent octapeptide effector of the classical RAS, acting via AT1R to induce vasoconstriction, sodium retention and fibrosis.

ACE2: An enzyme that converts Ang II to Ang 1-7, shifting the balance towards vasoprotective and anti-inflammatory signalling.

β-arrestin-biased agonist: A ligand that preferentially engages β-arrestin pathways over G protein signalling at a GPCR, yielding distinct cellular responses.

Mas receptor: A G protein-coupled receptor activated by Ang 1-7, mediating vasodilation and anti-remodelling effects in cardiovascular and renal tissues.

References

1. Four-week inhibition of the renin–angiotensin system in spontaneously hypertensive rats results in persistently lower blood pressure with reduced kidney renin and changes in expression of relevant gene networks. Cardiovascular Research (2024).
2. The alternative renin–angiotensin system in critically ill patients: pathophysiology and therapeutic implications. Critical Care (2023).
3. Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy. Scientific Reports (2017).