Clinical meaning
The renin-angiotensin-aldosterone system (RAAS) is a central hormonal cascade in blood pressure regulation. When renal perfusion drops, juxtaglomerular cells release renin, which cleaves angiotensinogen (from the liver) to angiotensin I. Angiotensin-converting enzyme (ACE), primarily in pulmonary endothelium, converts angiotensin I to angiotensin II (AT-II). AT-II acts on AT1 receptors to cause potent arteriolar vasoconstriction, stimulate aldosterone release from the adrenal cortex (increasing Na+/water reabsorption in the collecting duct via ENaC), promote ADH release, stimulate thirst, and induce cardiac and vascular remodeling (hypertrophy and fibrosis). ACE also degrades bradykinin, a vasodilator; ACE inhibitors therefore increase bradykinin (explaining both their vasodilatory benefit and the dry cough side effect). Endothelial dysfunction occurs when chronic hypertension reduces nitric oxide (NO) synthesis and increases endothelin-1, reactive oxygen species, and inflammatory cytokines, promoting atherosclerosis and further vascular stiffening.
Diagnosis & workup
Diagnostics & workup: - Plasma renin activity (PRA) and aldosterone: aldosterone-to-renin ratio (ARR) >30 screens for primary aldosteronism - Renal duplex ultrasound or CT/MR angiography for suspected renal artery stenosis (young woman with severe HTN or elderly with refractory HTN and rising creatinine on ACEi) - 24-hour urine metanephrines and catecholamines for pheochromocytoma screening - Overnight 1 mg dexamethasone suppression test or 24-hour urine cortisol for Cushing syndrome - BMP: hypokalemia suggests aldosteronism; elevated creatinine suggests renovascular or CKD-mediated HTN - TSH: both hyperthyroidism (systolic HTN) and hypothyroidism (diastolic HTN) cause secondary HTN - Echocardiography for LVH assessment and diastolic function evaluation