Effects of angiotensin II type 1 receptor antagonist on rats with septic shock.

AIMS: To investigate the effects of angiotensin II type 1 receptor (AT1R) antagonist, losartan, on rats with septic shock induced by endotoxin.

METHODS: Thirty male SD rats were randomly divided into 3 groups (10 for each group): rats were injected with normal saline in C group, lipopolysaccharide (LPS) of 12 mg kg(-1) intravenously in LPS group, and losartan of 50 mg kg(-1) intraperitoneally followed by LPS of 12 mg kg(-1) intravenously in LOS group. The plasma concentrations of nitric oxide (NO), malondialdehyde (MDA), IL-1β and TNF-α were measured 6 h after LPS administration. Then all the rats were sacrificed immediately before the aortas pectoralis were isolated. Inhibitor of NF-κB (IκB) mRNA and its mRNA expressions in aorta were detected.

RESULTS: The plasma concentrations of NO, MDA, IL-1β and TNF-α were all significantly elevated in LPS group compared with the control group (P<0.01), which were markedly reduced in LOS group (P<0.01). Both of the mRNA and protein expressions of IκB in aorta were downregulated after injection of LPS when compared with the control group (P<0.01). However, IκB mRNA and protein expressions in aorta in the LOS group were significantly higher than the LPS group (P<0.01).

CONCLUSION: AT1R antagonist, losartan, has a reverse effect at least partly on circulation dysfunction in rats with septic shock induced by endotoxin.