Cardioprotective effects of nitroparacetamol and paracetamol in acute phase of myocardial infarction in experimental rats.
We aimed to determine whether nitroparacetamol (NO-paracetamol) and paracetamol exhibit cardioprotective effects. Myocardial infarction (MI) was induced in rats, and drug treatment was started 1 wk before surgery. Mortality rate and infarct size at 2 days after MI were compared. Treatment groups included vehicle (saline), paracetamol (5 mg x kg(-1) x day(-1)) and NO-paracetamol (15 mg x kg(-1) x day(-1)). Mortality rates for vehicle (n = 80), paracetamol (n = 79), and NO-paracetamol (n = 76) groups were 37.5%, 21.5%, and 26.3%, respectively. Infarct size for the vehicle group was 44.8% (+/-6.1%) of the left ventricle (LV). For the paracetamol and NO-paracetamol groups, infarct size was 31.3% (+/-5.6%) and 30.7% (+/-8.1%) of the LV, respectively. Both paracetamol- and NO-paracetamol-treated groups showed increased activities of catalase and SOD compared with the vehicle group. They could attenuate endothelial, inducible, and neuronal nitric oxide synthase and cyclooxygenase-1 and -2 gene expression after MI. The observation indicates the potential clinical significance of the cardioprotective effects of these drugs.
Zhu
Yi Zhun
YZ
Dept. of Pharmacology, National Univ. of Singapore, Singapore 117597. phczhuyz@nus.edu.sg
Chong
Chew Lan
CL
Chuah
Shin Chet
SC
Huang
Shan Hong
SH
Nai
Huey Shan
HS
Tong
How Teng
HT
Whiteman
Matt
M
Moore
Philip K
PK
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002196:Capillaries / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D009566:Nitrates / Q000097:blood / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D009573:Nitrites / Q000097:blood; D010088:Oxidoreductases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D000082:Acetaminophen; D010088:Oxidoreductases; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; C478738:4-(nitroxy)butanoic acid 4-acetylaminophenyl ester