Olmesartan Ameliorates Organ Injury and Mortality in Rats With Peritonitis-Induced Sepsis

J Surg Res. 2022 Nov:279:526-532. doi: 10.1016/j.jss.2022.05.034. Epub 2022 Jul 19.

Abstract

Introduction: Sepsis and related complications lead to high morbidity and mortality in humans and animals. Olmesartan medoxomil (OLM), a nonpeptide angiotensin II type 1 receptor blocker, has antiinflammatory and antioxidative effects in various experimental animal models. The present study aimed to investigate whether OLM protects against sepsis in a clinically relevant model of polymicrobial sepsis induced by cecal ligation and puncture (CLP).

Methods: Sepsis was induced by CLP in anesthetized rats. OLM was administered intraperitoneally 3 h after CLP onset. Hemodynamic, biochemical, and inflammatory parameters were analyzed.

Results: The administration of OLM in CLP rats significantly improved their survival rate. Moreover, OLM mitigated CLP-induced hypotension and organ injury (indicated by biochemical parameters), but not tachycardia. OLM significantly reduced the plasma levels of interleukin-6 and nitric oxide.

Conclusions: OLM markedly attenuated CLP-induced hypotension and organ injury, and hence improved survival by inhibiting the inflammatory response and nitrosative stress in this clinically relevant model of sepsis.

Keywords: Inflammatory response; Nitric oxide; Olmesartan medoxomil; Organ injury; Polymicrobial sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers
  • Animals
  • Cecum
  • Disease Models, Animal
  • Humans
  • Imidazoles
  • Interleukin-6
  • Nitric Oxide
  • Olmesartan Medoxomil
  • Peritonitis* / complications
  • Peritonitis* / etiology
  • Rats
  • Rats, Wistar
  • Sepsis* / complications
  • Sepsis* / drug therapy
  • Tetrazoles

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Imidazoles
  • Interleukin-6
  • Tetrazoles
  • Nitric Oxide
  • Olmesartan Medoxomil
  • olmesartan