LIPID-PEROXIDATION INCREASES ARTERIAL CYCLOOXYGENASE ACTIVITY DURING PREGNANCY

OBJECTIVE: We tested the hypothesis that increased production of lipid peroxides (induced by a mild vitamin E deficiency) during pregnancy w ould after the cyclooxygenase pathway of arachidonate metabolism, resu lting in impaired endothelial-dependent vascular function. STUDY DESIG N: Mesenteric arteries from pregnant control (n = 12) and pregnant vit amin E-deprived (n = 12) Sprague-Dawley rats were studied in a myograp h. RESULTS: Surprisingly, endothelial-dependent relaxations to methach oline were enhanced in arteries from the pregnant vitamin E-deprived r ats compared with the pregnant control rats (mean effective concentrat ion producing a 50% response = 0.034 vs 0.046 mu mol/L, p < 0.05). In the arteries from the vitamin E-deprived rats this enhanced response w as blunted and the group difference eliminated in the presence of a cy clooxygenase inhibitor (1 mu mol/L meclofenamate, mean effective conce ntration producing a 50% response 0.057 vs 0.034 mu mol/L, p < 0.05) b ut had no effect on the arteries from the control pregnant rats. The t hromboxane A(2)-prostaglandin H-2 receptor blocker (1 mu mol/L SQ 2954 8) had no effect on the arteries from either group. Endothelial-indepe ndent relaxations to sodium nitroprusside were not affected by vitamin E deprivation. Arachidonic acid elicited less tension in the arteries from the vitamin E-deprived rats compared with the controls (at 10 mu mol/L: 0.41 vs 0.90 mN/mm, p < 0.01). Cyclooxygenase inhibition poten tiated the vasoconstrictor response only in the arteries from the vita min E-deprived rats (at 10 mu mol/L: 0.92 vs 0.41 mN/mm, p < 0.01) so that the group difference was eliminated. CONCLUSION: An elevation of lipid peroxides, mediated by a mild vitamin E deprivation, resulted in an increased cyclooxygenase-dependent vasorelaxation in the mesenteri c arteries of the pregnant rat.