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 would alter the cyclooxygenase pathway of arachidonate metabolism, resulting in impaired endothelial-dependent vascular function.


METHODS
Mesenteric arteries from pregnant control (n = 12) and pregnant vitamin E-deprived (n = 12) Sprague-Dawley rats were studied in a myograph.


RESULTS
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.


CONCLUSIONS
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.
Davidge
S T
ST
Department of Pediatrics, University of Cincinnati College of Medicine, Ohio.
Hubel
C A
CA
McLaughlin
M K
MK
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000502:physiology*; D008315:Malondialdehyde / Q000097:blood; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D016210:Methacholine Chloride / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014811:Vitamin E Deficiency / Q000378:metabolism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; D016210:Methacholine Chloride; D009599:Nitroprusside; D016718:Arachidonic Acid; D008315:Malondialdehyde; C045749:SQ 29548; D011451:Prostaglandin-Endoperoxide Synthases