Low-dose celecoxib improves coronary function after acute myocardial ischaemia in rabbits.
The role of celecoxib in cardiovascular events remains contentious. The aim of the present study was to investigate the effects of celecoxib in acute myocardial ischaemia (AMI) in rabbits in comparison with those of another non-steroidal anti-inflammatory drug, namely aspirin. Male New Zealand white rabbits were divided into four groups: (i) a sham-operated group; (ii) an AMI group, in which the left anterior descending coronary arteries were occluded for 60 min; (iii) the celecoxib + AMI group, pretreated with 3 mg/kg celecoxib, twice a day, for 3 days before AMI induction; and (iv) the aspirin + AMI group, pretreated with 12.5 mg/kg aspirin, twice a day, for 3 days before AMI induction. Haemodynamic parameters were monitored using a multichannel physiological recorder. Serum levels of creatine kinase (CK), malondialdehyde (MDA), cyclo-oxygenase-2 (COX-2), tumour necrosis factor (TNF)-α, total nitrate/nitrite (NO(x) ), nitric oxide synthase (NOS) and myocardial infarct size were determined. Changes in isometric tension of isolated coronary rings were recorded by a myograph system. Compared with the sham group, the AMI group had lower blood pressure, higher left ventricular (LV) end-diastolic pressure, depressed maximum dP/dt of LV pressure, a larger infarct size and higher CK and MDA levels. Celecoxib, but not aspirin, pretreatment significantly ameliorated these effects of AMI. Celecoxib reversed AMI-induced increases in COX-2 levels to a similar extent as aspirin. Pretreatment with celecoxib resulted in a significant reduction in TNF-α levels and an increase in NO(x)  and NOS levels compared with the AMI group. The dysfunctional vasoconstriction and vasodilation of coronary arteries were ameliorated by celecoxib administration. 4. In conclusion, the experimental evidence suggests that celecoxib exerts its protective effects in a COX-independent manner.
Department of Pharmacology, Xi'an Jiaotong University, College of Medicine, Xi'an, China.
Ming
M
Zhao
Xi
X
He
Mei
M
Zhao
Xue-Yuan
XY
Bi
Hong-Li
HL
Zhang
Xiao-Jiang
XJ
Yu
Jin-Jun
JJ
Liu
Dong-Ling
DL
Li
Xin
X
Ma
Wei-Jin
WJ
Zang
D000208:Acute Disease; D000818:Animals; D000068579:Celecoxib; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology*; D011720:Pyrazoles / Q000008:administration & dosage*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage*
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib