Lipid peroxidation increases arterial cyclooxygenase activity during pregnancy.

Abstract

We tested the hypothesis that increased production of lipid peroxides (induced by a mild vitamin E deficiency) during pregnancy would alter the cyclooxygenase pathway of arachidonate metabolism, resulting in impaired endothelial-dependent vascular function. Mesenteric arteries from pregnant control (n = 12) and pregnant vitamin E-deprived (n = 12) Sprague-Dawley rats were studied in a myograph. Surprisingly, endothelial-dependent relaxations to methacholine were enhanced in arteries from the pregnant vitamin E-deprived rats compared with the pregnant control rats (mean effective concentration producing a 50% response = 0.034 vs 0.046 mumol/L, p < 0.05). In the arteries from the vitamin E-deprived rats this enhanced response was blunted and the group difference eliminated in the presence of a cyclooxygenase inhibitor (1 mumol/L meclofenamate, mean effective concentration producing a 50% response 0.057 vs 0.034 mumol/L, p < 0.05) but had no effect on the arteries from the control pregnant rats. The thromboxane A2-prostaglandin H2 receptor blocker (1 mumol/L SQ 29548) had no effect on the arteries from either group. Endothelial-independent 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 mumol/L: 0.41 vs 0.90 mN/mm, p < 0.01). Cyclooxygenase inhibition potentiated the vasoconstrictor response only in the arteries from the vitamin E-deprived rats (at 10 mumol/L: 0.92 vs 0.41 mN/mm, p < 0.01) so that the group difference was eliminated. An elevation of lipid peroxides, mediated by a mild vitamin E deprivation, resulted in an increased cyclooxygenase-dependent vasorelaxation in the mesenteric arteries of the pregnant rat.