Catechins blunt the effects of oxldl and its primary metabolite phosphatidylcholine hydroperoxide on endothelial dysfunction through inhibition of oxidative stress and restoration of eNOS in rats

Background/Aims: We explored the effects of catechins (decaffeinated green tea extracts containing (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate and (-)-epigallocatechin gallate) on atherosclerosis risk factors, oxidized low-density lipoprotein (oxLDL) and its primary metabolite, phosphatidylcholine hydroperoxide (PCOOH) induced oxidative injury in cultured endothelial cell line and rats. Methods: We used endothelial cell line and male Wistar rats to determine the effect of catechins on oxLDL or PCOOH induced oxidative injury including apoptosis, H₂O₂ level, vascular responses and urinary 8-isoprostane and nitrite/nitrate concentration. Plasma catechins concentration was determined by a CoulArray HPLC. Responses of aortic and renal vasoconstriction were evaluated by a transonic meter and a full-field laser perfusion imager. Results: PCOOH administration significantly increased H₂O₂ amounts and cell apoptosis and decreased endothelial nitric oxide synthase (eNOS) expression in the cultured endothelial cells. Catechins pretreatment significantly reduced PCOOH-elevated H₂O₂ amounts, endothelial cell apoptosis and partly recovered eNOS expression. Intravenous administration of oxLDL, PCOOH or H₂O₂, not native LDL, significantly decreased renal and aortic blood flow associated with enhanced ICAM-1 expression and 4-hydroxynoneal (4-HNE) accumulation, and decreased eNOS expression in the male Wistrar rats. One hour after oral intake of green tea extracts, 4 peaks of catechins were found in the rat plasma. The increased plasma catechins significantly inhibited oxLDL-, PCOOH- or H₂O₂-induced renal and aortic vasoconstriction, decreased urinary 8-isoprostane levels, renal ICAM-1 expression and 4-HNE accumulation, and restored nitrite/nitrate amounts and eNOS activity. Conclusions: Our data suggests that catechins pretreatment decrease PCOOH-induced endothelial apoptosis and arterial vasoconstriction through the action of H₂O₂ inhibition and eNOS restoration.