Candesartan improves survival following severe hypovolemia in pigs; a role for the angiotensin II type 2 receptor?

Mats Laesser, Emma Spak, Sara Ewert, Anders Aneman, Lars Fandriks*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: To investigate the involvement of intestinal angiotensin II type 2 receptors in the outcome of acute severe hypovolemia as well as systemic and regional mesenteric hemodynamics and intestinal mucosal functions in anesthetized pigs. Design and setting: Prospective, interventional animal study in a university research laboratory. Subjects: 53 landrace pigs, 28-35 kg. Interventions: 30+30% or 20+20% hemorrhage of estimated total blood volume followed by retransfusion performed in untreated controls, in animals treated with the angiotensin II type 1 receptor blocker candesartan or with a combination of candesartan and the angiotensin II type 2 receptor blocker PD123319. Measurements and results: Following 30+30% hemorrhage the candesartan-treated animals attained a significantly higher survival rate than controls and animals treated with PD123319 in combination with candesartan. Less pronounced hemorrhage (20+20%) resulted in no mortality and functional variables were assessed. A significantly higher output of jejunal intraluminal nitric oxide occurred during hypovolemia in the candesartan treated group than in controls and animals that received PD123319 in combination with candesartan. Jejunal transmucosal potential difference was significantly better preserved after retransfusion in candesartan-treated animals than in controls. Expression of angiotensin II type 2 receptors in intestinal tissue was significantly higher in animals surviving the 30+30% hemorrhage than in nonsurvivors. Conclusions: Lethal circulatory failure is possibly influenced by use of angiotensin receptor ligands, and activation of intestinal angiotensin II type 2 receptors may play a significant role in improving the outcome of severe hypovolemia.

Original languageEnglish
Pages (from-to)1109-1115
Number of pages7
JournalIntensive Care Medicine
Volume31
Issue number8
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Angiotensin II receptors
  • Candesartan
  • Gastrointestinal
  • Hemorrhage
  • PD123319
  • Renin-angiotensin system

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