From the Guidelines
The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in regulating blood pressure, fluid balance, and vascular resistance, and its inhibition is a cornerstone of treating hypertension, heart failure, and kidney disease, as evidenced by the latest guidelines and studies 1.
Role of RAAS Inhibition
The RAAS pathway involves the conversion of angiotensinogen to angiotensin I by renin, and then to angiotensin II by angiotensin-converting enzyme (ACE), which stimulates aldosterone release and increases blood pressure. Inhibiting this pathway using medications like ACE inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists can reduce blood pressure and provide organ protection.
Clinical Applications
RAAS inhibition is recommended for patients with:
- Hypertension and albuminuria (ACR ≥30 mg/g) 1
- Heart failure with reduced ejection fraction (HFrEF) 1
- Chronic kidney disease (CKD) 1
- Diabetes and CKD 1
Medications and Dosages
Commonly used medications for RAAS inhibition include:
- ACE inhibitors (e.g., lisinopril 10-40 mg daily)
- ARBs (e.g., losartan 25-100 mg daily)
- Aldosterone antagonists (e.g., spironolactone 25-50 mg daily)
Side Effects and Monitoring
Side effects of RAAS inhibition may include:
- Cough with ACE inhibitors
- Hyperkalemia
- Reduced kidney function, particularly in patients with renal artery stenosis Regular monitoring of blood pressure, kidney function, and potassium levels is essential when using these medications 1.
From the FDA Drug Label
- 1 Mechanism of Action Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)] is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system, and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex
The role of the Renin-Angiotensin-Aldosterone System (RAAS) is to:
- Regulate blood pressure through vasoconstriction
- Stimulate aldosterone secretion, which is involved in the pathophysiology of hypertension Key components of the RAAS include:
- Angiotensin II: a potent vasoconstrictor and primary vasoactive hormone
- Angiotensin converting enzyme (ACE): catalyzes the formation of angiotensin II from angiotensin I
- Aldosterone: a hormone involved in blood pressure regulation 2
From the Research
Role of the Renin-Angiotensin-Aldosterone System (RAAS)
The RAAS plays a crucial role in regulating blood pressure, fluid, and electrolyte balance in the body. It is also involved in the pathophysiology of cardiovascular and kidney diseases 3, 4, 5, 6, 7.
- The RAAS is a hormonal cascade that functions in the homeostatic control of arterial pressure, tissue perfusion, and extracellular volume 7.
- Dysregulation of the RAAS contributes to the development of hypertensive cardiovascular disease and related conditions 7.
- The RAAS is initiated by the regulated secretion of renin, which catalyzes the hydrolysis of angiotensin (Ang) I from the N-terminus of angiotensinogen 7.
- Ang I is then hydrolyzed by angiotensin-converting enzyme (ACE) to form Ang II, a potent vasoconstrictor and the primary active product of the RAAS 7.
Therapeutic Targeting of the RAAS
The RAAS is a key therapeutic target in the treatment of heart failure, hypertension, and kidney diseases.
- Blockade of the RAAS with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-II (ANG-II) receptor blockers (ARBs) lowers blood pressure, decreases morbidity and mortality in patients with chronic heart failure, and decreases proteinuria and the rate of decline in renal function in patients with chronic kidney disease 3.
- Combinations of ACEIs and ARBs have been shown to be superior to either agent alone for some, but not all, composite cardiovascular and kidney outcomes 3.
- Direct renin inhibitors (DRIs) and mineralocorticoid receptor blockers (MRBs) are alternative combination strategies that may offer novel ways to more fully suppress the RAAS 3, 7.
Clinical Evidence and Guidelines
Clinical evidence supports the use of RAAS inhibitors in the treatment of hypertension, heart failure, and kidney diseases.
- The efficacy of ACEIs and ARBs has been promoted to extend beyond what could be explained by blood pressure reduction alone, but closer scrutiny of outcome data shows little evidence for this 6.
- Guideline recommendations and future perspectives emphasize the importance of RAAS inhibition in the management of cardiovascular and kidney diseases 6.