COENZYME Q(10) PROTECTS CORONARY ENDOTHELIAL FUNCTION FROM ISCHEMIA-REPERFUSION INJURY VIA AN ANTIOXIDANT EFFECT

Background. Cardiac ischemia reperfusion (I/R) injury causes coronary vascular dysfunction. Coenzyme Q(10) (CoQ), which preserves cardiac me chanical function after I/R, recently has been recognized as a free ra dical scavenger We hypothesized that CoQ protects coronary vascular re activity after I/R via an antioxidant mechanism. Methods. Rats were pr etreated with either CoQ (20 mg/kg intramuscular and 10 mg/kg intraper itoneal [CoQ group]) or a vehicle (Control) before the experiment. Iso lated perfused rat hearts were subjected to 25 minutes of global normo thermic ischemia and 40 minutes of reperfusion. The reperfusion-induce d oxidative burst was directly assessed by lucigenin enhanced chemilum inescence. Coronary flow was measured at equilibration and after reper fusion with or without bradykinin, an endothelium-dependent vasodilato r, and sodium nitroprusside (SNP), an endothelium-independent vasodila tor. The effect of intracoronary infusion of hydrogen peroxide (H2O2 0 .1 mu mol/gm body weight given over 5 minutes), simulating the free ra dical burst after I/R, also was evaluated. Results. I/R decreased the bradykinin-induced change in coronary flaw (-5% +/- 4% versus 26% +/- 3% at equilibration; p < 0.05) and the SNP-induced change (+20% +/- 6% versus +56% +/- 5% at equilibration; p < 0.05). The coronary vasculat ure after H2O2 infusion revealed a similar loss in vasodilatory respon siveness (+4% +/- 4% in response to bradykinin, +35% +/- 8% in respons e to SNP; p < 0.05 versus equilibration). Pretreatment with CoQ improv ed BK-induced vasorelaxation after I/R (+12% +/- 2%; p < 0.05 versus c ontrol I/R) or H2O2 infusion (18% +/- 4%; p < 0.05 versus control I/R) but failed to improve SNP-SNP-induced vasorelaxation. The CoQ pretrea tment decreased the I/R-induced maximal free radical burst (9.3 +/- 0. 8 x 10(3) cpm versus 11.5 +/- 1.1 x 10(3) cpm; p < 0.05) during the ea rly period of reperfusion. Conclusions. Endothelium-dependent vasorela xation is more sensitive than endothelium-independent relaxation to I/ R injury. Via a direct antioxidant effect, CoQ preserved endothelium-d ependent vasorelaxation by improving tolerance to I/R injury.