RAAS Is Key
In hypotension from vasoplegia, can addressing RAAS dysfunction open the door to hemodynamic stability? In hypotension from vasoplegia, can addressing RAAS dysfunction open the door to hemodynamic stability?

Hypotension from vasoplegia—a critical condition
that can persist when RAAS becomes dysregulated
and fails to restore hemodynamic stability1,2

Vasoplegia is marked by refractory hypotension, most often surfacing in the hours following CPB3

Profound vasodilation icon

Profound vasodilation

Endothelial injury reduces the expression and activity of ACE, leading to impaired ANG II formation and excess production of vasodilatory angiotensin metabolites1,4-6

Impaired perfusion icon

Impaired perfusion

Despite high cardiac output, hypotension leads to inadequate tissue perfusion, reduced oxygen extraction, and tissue hypoxia4,6,7

Multi-organ damage icon

Multi-organ damage

Sustained hypotension drives
damage across vital end organs,
including the kidneys, heart, and lungs, that can ultimately lead to organ failure6,7

Early aggressive treatment of vasoplegia-related hypotension is vital8

RAAS pathway dysfunction drives hypotension,
a hallmark of vasoplegia pathophysiology1

Under normal conditions, the RAAS
pathway increases blood pressure in
response to hypotension

  • The kidneys release renin into the bloodstream in response to low blood pressure9
  • Renin cleaves angiotensinogen, produced in the liver, to ANG I9
  • ACE, expressed by pulmonary endothelial cells, converts ANG I into ANG II9
ANG II maintains hemodynamic stability by

• Inducing vasoconstriction9
• Triggering norepinephrine and vasopressin release9,10

How RAAS pathway dysfunction
perpetuates hypotension

  • The kidneys release renin into the bloodstream in response to low blood pressure9
  • Renin cleaves angiotensinogen, produced in the liver, to ANG I9
  • In vasoplegia, endothelial injury in the lungs or bypass of the lungs during CPB reduces the expression and activity of ACE, thereby limiting conversion of ANG I into ANG II and leading to excess production of vasodilatory angiotensin metabolites11,12
ANG II depletion contributes to hypotension by

• Preventing vasoconstriction9
• Stimulating renin release and leading to excess production of vasodilatory angiotensin metabolites9,12

RAAS dysfunction limits ANG II production—impairing blood pressure restoration in vasoplegia1

ACE=angiotensin-converting enzyme; ANG=angiotensin; CPB=cardiopulmonary bypass; RAAS=renin-angiotensin-aldosterone system.

References: 1. Klijian A, et al. J Cardiothorac Vasc Anesth. 2021;35(1):51-58. 2. Ltaief Z, et al. J Clin Med. 2022;11(21):6407. 3. Busse LW, et al. Crit Care. 2020;24(1):36. 4. Boisramé-Helms J, et al. Curr Vasc Pharmacol. 2013;11(2):150-160. 5. Miranda M, et al. Am J Physiol Heart Circ Physiol. 2016;311(1):H24-H35. 6. Parrillo JE, et al. Ann Intern Med. 1990;113(3):227-242. 7. Annane D, et al. Lancet. 2005;365(9453):63-78. 8. Tsiouris A, et al. Gen Thorac Cardiovasc Surg. 2017;65(10):557-565. 9. Fountain JH, et al. StatPearls; 2023. Accessed January 14, 2025. https://www.ncbi.nlm.nih.gov/books/NBK470410/ 10. Tibi S, et al. J Clin Med. 2023;12(14):4566. 11. Papazisi O, et al. Cardiovasc Drugs Ther. 2022;36(4):739-748. 12. Bellomo R, et al. Am J Respir Crit Care Med. 2020;202(9):1253-1261.