The Renin–Angiotensin–Aldosterone System (RAAS) governs blood pressure, intravascular volume, and electrolyte balance — processes central to anesthetic physiology. Perioperative modulation of RAAS by disease and drugs underlies common anesthesia problems: induction hypotension, vasoplegia, volume derangements, and dyskalemias. This revised article integrates molecular detail with immediate clinical application, adds management algorithms, relevant drug interaction tables, diagnostic phenotypes, and practical clinical pearls for anesthesia clinicians.
In anesthesia, the RAAS determines whether a patient’s blood pressure gracefully dips or catastrophically collapses at induction. Every vasopressor choice and every fluid decision reflects an interaction with this hidden hormonal circuit. Understanding RAAS at the molecular level allows the anesthesiologist to Predict → Prevent → Personalize (P³)hemodynamic care.
Teaching diagram placeholder: RAAS during anesthesia induction — flow diagram showing (1) induction agent → ↓ sympathetic tone → effect on JGA/macula densa → renin release change → Ang II/aldosterone response → hemodynamic consequence.
RAAS activation integrates three renal sensors:
Intrarenal baroreceptors (afferent arteriole): detect decreased renal perfusion pressure and directly stimulate renin release.
β₁-adrenergic receptors on juxtaglomerular (JG) cells: sympathetic activation increases renin.
Macula densa sensing of tubular Na⁺ (and chloride): reduced distal NaCl stimulates renin via paracrine mediators (adenosine, prostaglandins) and ATP signaling.
Clinical note: macula densa–derived ATP/adenosine normally constrains renin—drugs or disease that alter tubular flow (diuretics, low cardiac output) will shift this balance.
Volatile anesthetics (e.g., sevoflurane) reduce renal sympathetic tone and may modulate NO signaling, thereby blunting β₁-mediated renin release. Practically, this means the initial phase of the RAAS response to hypotension under anesthesia is often attenuated.
Clinical implication: Under volatile anesthesia, compensation via RAAS is slower; vasopressor support may therefore be needed earlier.
Renin cleaves hepatic angiotensinogen → angiotensin I → ACE (mostly pulmonary endothelium) → angiotensin II (Ang II). Ang II is the primary effector with diverse vascular, renal, and central effects.
AT₁ receptor (AT₁R): Gq-coupled → PLC → IP₃/DAG → intracellular Ca²⁺ release → vasoconstriction; promotes aldosterone, sympathetic facilitation, oxidative stress.
AT₂ receptor (AT₂R): often counter-regulatory — promotes vasodilation, antiproliferative effects, and may increase bradykinin/NO pathways.
Clinical relevance (ACEI/ARB therapy): Chronic ACE inhibition or ARB use can shift signaling balance toward AT₂R-mediated vasodilation. This contributes to reduced vascular responsiveness to catecholamines — a mechanistic component of ACEI-related refractory hypotension.
ACE also degrades bradykinin. ACE inhibition increases bradykinin levels → vasodilation and (rarely) angioedema — both relevant to the...
