Carvedilol improved diabetic rat cardiac function depending on antioxidant ability.
The risk for cardiovascular disease is significantly high in diabetes mellitus. Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has a close connection with antagonizing oxidative stress destroy in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant and free radical scavenger properties. To study the effect of carvedilol on the antioxidant status and expression of Bcl-2 in healthy and diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage (1 or 10mg/kg/d) carvedilol-administrated for 5 weeks, hemodynamic parameters, the levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and expression of Bcl-2 mRNA in the cardiac tissues of all six groups were measured. Diabetic rats had higher left ventricular end diastolic pressure (LVEDP), lower maximal rate of rise/fall left ventricle pressure development and decline (+/-dP/dtmax). These parameters were improved by administration of carvedilol. Diabetic rats showed elevated MDA level and CAT activity, but lower activities of SOD and GSH-Px. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicate that carvedilol improves cardiac function via its antioxidant property in diabetic rats partly.
Huang
He
H
Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310016, China. huanghell@hotmail.com
Shan
Jiang
J
Pan
Xiao-Hong
XH
Wang
Hui-Ping
HP
Qian
Ling-Bo
LB
Xia
Qiang
Q
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D000959:Antihypertensive Agents; D000975:Antioxidants; D001786:Blood Glucose; D002227:Carbazoles; D011412:Propanolamines; D019253:Proto-Oncogene Proteins c-bcl-2; D000077261:Carvedilol