Protective effect of urantide against myocardial ischemia-reperfusion injury
- VernacularTitle:Urantide对心肌缺血/再灌注损伤的保护作用
- Author:
Hua YAO
;
Junyan ZHANG
;
Zhiwu CHEN
- Publication Type:Journal Article
- Keywords:
urantide;
myocardial ischemia reperfusion injury;
ischemic preconditioning;
nitric oxide;
malondialdehyde;
inducible nitric oxide synthase
- From:
Chinese Pharmacological Bulletin
1986;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the protective effect of the potent UT receptor(urotensin Ⅱ receptor,UTS2R)antagonist-urantide against myocardial ischemia-reperfusion(I/R)injury and its probable mechanisms in rats.Methods Rat myocardial I/R injury was induced by ligating and untying the left anterior descending coronary artery.The rats were randomly assigned into 6 groups:sham group,model group,urantide 3 ?g?kg-1 group,urantide 10 ?g?kg-1 group,urantide 30 ?g?kg-1 group and Ver(Verapamil)1.6 mg?kg-1 group.All animals except sham group were subjected to 30 min of occlusion and 60 min of reperfusion.Urantide or Ver was given ten minutes before occlusion through intravenous drug perfusion.Heart rate(HR)and the ST segment change of electrocardiogram(ECG)were recorded.The content of malondialdehyde(MDA)and nitric oxide(NO),and the activity of lactate dehydrogenase(LDH)and nitric oxide synthase(NOS)in blood serum were measured.Infarct size(IS),as a percentage of the area at risk(AAR),was determined by Evans blue and TTC double staining.The expression of iNOS protein was detected by western blotting.Results The results demonstrated that during the process of I/R,HR decreased significantly whereas ST segment of ECG markedly elevated.After I/R,MDA content and LDH activity in blood serum increased significantly,while total NO content and total NOS activity decreased sharply.Urantide(10,30 ?g?kg-1)had no significant effect on HR changes,but could markedly inhibit the elevation of ST segment of ECG,MDA content and LDH activity,and inhibit the decline of total NO content and total NOS activity,at the same time decrease I/R induced IS/AAR.But 3 ?g?kg-1 urantide had no significant effect on above indexes.Except for this,urantide(10,30 ?g?kg-1)down-regulated the I/R induced expression of iNOS.Conclusions Our findings indicate that urantide has a protective effect against myocardial I/R injury in rats.The cardio-protective involves the inhibition of lipid peroxidation and the stimulation of NO release.
