Prevention of aminoguanidine against impairment of endothelium-dependent relaxation induced by glycosylated proteins in isolated rat aorta
- VernacularTitle:氨基胍对糖基化蛋白损伤大鼠血管内皮功能的影响
- Author:
Sihai FU
;
Yan XIONG
;
Yunfeng FU
;
Zheng GUO
;
- Publication Type:Journal Article
- Keywords:
aminoguanidine;
advanced glycation end products;
superoxide dismutase;
diethyldithiocarbamate;
endothelium dependent relaxation;
thoracic aorta;
rat
- From:
Chinese Pharmacological Bulletin
2003;0(07):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM This study was designed to investigate the effect of aminoguanidine, an inhibitor of the glycosylated proteins formation, on the impairment of endothelium dependent relaxation induced by advanced glycation end products (AGE) in isolated rat thoracic aorta and its possible mechanisms. METHODS Exogenous glycosylated bovine serum albumin (AGE BSA) was prepared. Aortic rings were exposed to AGE BSA for 60 min to induce the impairment of endothelium dependent vasodilatation. In the drug treated groups, aortic rings were incubated with drug for 15 min and then exposed to AGE BSA for another 60 min in the presence of the drug. Vasodilator responses to acetylcholine (ACh) or sodium nitroprusside (SNP) of aortic rings were measured by isometric tension recording after drug treatment. RESULTS AGE BSA significantly inhibited the endothelium dependent relaxation in response to ACh, but did not affect endothelium independent relaxation in response to SNP. Pre incubation of aortic rings with aminoguanidine(50～500 ?mol?L -1 ) for 15 min and co incubation of aortic rings with AGE BSA for another 60 min markedly attenuated the inhibition of endothelium dependenet relaxation induced by AGE BSA in a dose dependent manner. Superoxide diamutase (SOD, 2?10 5 U?L -1 ), a scavenger of superoxide anions, also prevented the inhibition of endothelium dependent relaxation, which is similar to the effect of 500 ?mol?L -1 aminoguanidine. Furthermore, aminoguanidine (500 ?mol?L -1 ) also reversed impairment of endothelium dependent relaxation of rat aortic ring induced by endogenous oxygen free radicals generated by diethyldithiocarbamate (DETC, 10 ?mol?L -1 ) via inhibiting intracellular SOD. CONCLUSION Aminoguanidine can protect rat aortic endothelium against damage due to AGE BSA, and the beneficial effect of aminoguanidine may relate to its antioxidant properties.
