Effects of candesartan and enalaprilat on the organ-specific microvascular permeability during haemorrhagic shock in rats

Jan Schumacher*, M. R. Puchakayala, K. Binkowski, W. Eichler, A. Dendorfer, K. F. Klotz

*Korrespondierende/r Autor/-in für diese Arbeit
9 Zitate (Scopus)


Background. To counteract the contribution of angiotensin II to shock-induced ischaemic organ damage pharmacologic blockade of the renin-angiotensin-system (RAS) is currently under investigation. To evaluate potential side-effects of RAS blockade regarding capillary leak, we studied alterations in microvascular permeability in various organs during haemorrhagic shock (HS) in rats pretreated with candesartan (AT1-receptor antagonism) or enalaprilat (ACE-inhibition). Methods. Thirty-eight instrumented and anaesthetized animals received either candesartan, enalaprilat or placebo. Within each of the three groups 6-7 animals were exposed to HS and 6 animals of each group served as normovolaemic controls. After 30 min of shock, 50 mg kg-1 Evans blue (EB) was injected i.v. followed by a distribution period of 20 min. Exsanguination was performed with saline, before harvesting organs to quantify albumin-bound EB extravasation. Results. To reduce cardiac output from 37.5(1.3) to 20.4(1.1) ml min-1[mean(sem)] in the shock groups, withdrawal of 4.0(0.25) ml[mean (sem)] blood was necessary. Simultaneously mean arterial pressure decreased from 77.5(3.2) to 36.1(2) mm Hg. Serum lactate increased significantly from 1.3(0.1) to 3.5(0.24) mmol litre-1. Treatment with candesartan increased EB extravasation in the kidney in normovolaemic controls. Specific AT1 and ACE-blockade before acute nonresuscitated HS significantly increased EB extravasation in the rat ileum by 53 and 66%, respectively. Conclusion. This observation of increased microvascular albumin extravasation should be borne in mind for any interventional use of candesartan or enalaprilat during circulatory stress.

ZeitschriftBritish Journal of Anaesthesia
Seiten (von - bis)437-443
PublikationsstatusVeröffentlicht - 01.01.2006

Strategische Forschungsbereiche und Zentren

  • Profilbereich: Zentrum für Bevölkerungsmedizin und Versorgungsforschung (ZBV)


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