Why is the Renin-Angiotensin-Aldosterone System (RAAS) increased in patients with hypertension?

Why RAAS is Increased in Hypertension

RAAS is not universally "increased" in all hypertension—rather, it is inappropriately activated or dysregulated in specific secondary causes of hypertension, while in essential hypertension, RAAS components may be normal or even suppressed but still contribute to blood pressure elevation through impaired feedback mechanisms.

Primary Mechanisms of RAAS Activation in Hypertension

Renovascular Hypertension

• Renal artery stenosis decreases renal perfusion pressure, which directly activates RAAS as a compensatory mechanism to restore kidney perfusion 1
• When renal blood flow is compromised, the juxtaglomerular apparatus releases renin, converting angiotensinogen to angiotensin I, which is then converted to angiotensin II—a potent vasoconstrictor that raises systemic blood pressure 1
• In unilateral renal artery stenosis, this creates renin-mediated vasoconstriction hypertension, though renin elevations may moderate in chronic phases 1
• Very elevated renin levels raise clinical suspicion for renovascular hypertension, though this finding is not highly sensitive 1

Primary Aldosteronism

• Primary aldosteronism represents inappropriate aldosterone excess with suppressed renin—not increased RAAS activation 1
• This condition affects approximately 20% of patients with resistant hypertension and 6-13% of general hypertensive populations depending on severity 1
• The stimulus for aldosterone excess has not been fully identified, but obesity-related mechanisms may include adipocyte-released secretagogues that stimulate aldosterone independent of angiotensin II 1
• Importantly, serum potassium is rarely low in primary aldosteronism, indicating hypokalemia is a late manifestation 1

RAAS Dysregulation Rather Than Simple Activation

Impaired Feedback Inhibition

• In many hypertensive patients, the problem is not increased RAAS but rather impaired negative feedback regulation 1
• Normal physiology dictates that elevated blood pressure should suppress renin release through negative feedback 2
• When angiotensin II or aldosterone levels are inappropriately elevated relative to blood pressure, their antinatriuretic effects shift pressure natriuresis to higher levels, necessitating increased blood pressure to maintain sodium balance 2
• Some hypertensive patients demonstrate higher plasma renin concentrations despite elevated blood pressure, suggesting impaired feedback inhibition 1

Obesity and Metabolic Factors

• Obesity is associated with generalized RAAS activation through unclear mechanisms 1
• Adipocytes may release factors that stimulate aldosterone release independent of the traditional angiotensin II pathway 1
• Preliminary evidence links aldosterone excess to obstructive sleep apnea in resistant hypertension patients 1

Tissue-Level RAAS Activity

Local Tissue Production

• Components of RAAS (angiotensin II, ACE, and aldosterone) are synthesized locally in atrial myocardium and increase during pathological states 1
• Aging, environmental stress, inflammation, and RAAS activation cause oxidative damage in cardiovascular tissues 1
• Tissue-level RAAS activation promotes structural remodeling, fibrosis, inflammation, and oxidative stress beyond simple blood pressure effects 3

Intrarenal Effects

• Angiotensin II has direct intrarenal effects on tubular sodium transport and potent efferent arteriolar constriction 2
• These intrarenal actions are quantitatively more important than aldosterone changes in regulating renal excretion and arterial pressure 2
• The efferent arteriolar constriction increases tubular reabsorption by altering peritubular capillary forces 2

Clinical Implications for Specific Populations

Bilateral Renal Artery Stenosis

• In bilateral stenosis or stenosis to a solitary kidney, the physiology shifts from renin-mediated vasoconstriction to predominantly extracellular fluid volume expansion 1
• ACE inhibitors or ARBs can cause acute renal failure in these patients by decreasing transglomerular hydrostatic pressure and glomerular filtration rate 1

Obstructive Sleep Apnea

• OSAS is present in up to 60% of resistant hypertension patients and is associated with RAAS activation through sympathetic nervous system stimulation 1
• OSAS should be suspected in patients with non-dipping or reverse-dipping blood pressure patterns 1

Important Caveats

The concept that RAAS is simply "increased" in hypertension is oversimplified—the reality involves:

• Inappropriate activation relative to blood pressure status (not absolute elevation) 1
• Impaired negative feedback mechanisms that fail to suppress RAAS despite elevated pressure 1
• Tissue-specific RAAS activation that occurs independently of circulating levels 1, 3
• Secondary causes (renovascular disease, primary aldosteronism) where RAAS dysregulation is the primary mechanism 1

In essential hypertension, RAAS components may actually be normal or suppressed in absolute terms, but remain inappropriately elevated relative to the patient's blood pressure status 4, 5.