Novel aspects of the renin-angiotensin-aldosterone system in septic shock

Sepsis and septic shock are associated with high mortality rates and constitute the primary cause of death in intensive care units worldwide. Activation of the circulating renin-angiotensin-aldosterone system (RAAS) is an early event, and elements of the RAAS, including renin, Angiotensinogen, and ACE2, may be predictive of worse outcomes and higher mortality that reflect a failure to increase the circulating levels of the vasopressor Ang II. Emerging evidence suggests that dipeptidyl peptidase III (DPP3) is involved in the metabolism of Ang II, and higher DPP3 in septic shock may contribute to lower Ang II tone. The current review considers the role of a dysfunctional RAAS to maintain blood pressure and adequate tissue perfusion in septic shock.