COX-2 inhibitor protects rat hearts against oxidative stress through endothelial function improvement and NO enhancement.

The study was to explore whether cyclooxygenase 2 (COX-2) inhibitor could protect the myocardial function against oxidative stress injury in rat hearts and to investigate its mechanisms. Isolated rat hearts perfused by the Langendorff method were exposed to H₂O₂ (140|ÌM/L), after that coronaries were precontracted with U-46619, and then the response to the endothelium-dependent vasodilator 5-HT and endothelium-independent SNP were evaluated. Exposure hearts to H₂O₂ for 20 min, systolic function were reduced. Pretreatment with COX-2 inhibitor nimesulide (5|ÌM/L) enhanced the LVDP and ¡ÀdP/dtmax, which could be abolished by NOS inhibitor L-NAME. The vasodilatation produced by 5-HT and SNP in H₂O₂ group was significantly less than in that of control group. Pretreatment with nimesulide antagonized the decrease in endothelium-dependent vasodilatation, but had no effect on the decline in endothelium-independent vasodilatation. The concentration of 6-keto PGF_1:À was no different among all groups. These data suggest that nimesulide could improve myocardial function in rat hearts suffered from oxidative stress. The mechanisms may be through endothelial function improvement and NO enhancement, but not via inhibiting COX-2 activity. [ABSTRACT FROM AUTHOR]