Improvement of vascular hyporesponsiveness in rats with sepsis by pro-tein C activator from Agkistrodon acutus venom / 中国病理生理杂志

ABSTRACT

AIM: To investigate the effects of protein C activator (PCA) from Agkistrondon acutus venom ( AAV) on the tension of thoracic aorta rings isolated from the rats with sepsis.METHODS:The model of sepsis was es-tablished by intraperitoneal injection of lipopolysaccharide ( LPS) .SD rats were randomly divided to 6 groups ( n=6 )sham group, LPS group, PCA intervention group (LPS+PCA, PCA at doses of 0.1 mg/kg, 0.3 mg/kg and 0.6 mg/kg) and LPS+polymyxin B (at dose of 0.2 mg/kg) group.Using perfusion experiment in vitro, the tension of the aortic rings was measured by biological signal analytical system.RESULTS:The values of MABP, HR, LVDP and ±dp/dtmax were significantly lower in LPS group than those in sham group and LPS+PCA groups.Compared with sham group, the relaxa-tion response to acetylcholine ( ACh) and the contractile response of aorta rings induced by phenylephrine ( Phe) were sig-nificantly decreased in LPS group, which were increased significantly in PCA intervention group ( especially at dose of 0.6 mg/kg) compared with LPS group.The dose-response curve of aorta contraction with denuded endothelium induced by Phe shifted down significantly in LPS group compared with sham group, and no significant difference between LPS group and PCA intervention group was observed.Also no statistical difference was found in non-endothelium dependent relaxation of aortic rings induced by sodium nitroprusside among the groups.Pretreatment of N-nitro-L-arginine methl ester and methyl-ene blue increased the contraction amplitude of aortic rings induced by Phe.CONCLUSION:PCA from AAV effectively reverses the hypoergia of the vessels in rats with sepsis through protecting vascular endothelium, the mechanism of which may be mediated by inhibiting NO-GC-cGMP signal transduction pathway.