Dysfunction of the cyclo-oxygenase pathway in the foetoplacental circulation in Type 1 diabetes mellitus.

AIM: In diabetes, perinatal morbidity is significantly increased. This may partly be related to functional changes in the foetoplacental vascular bed. In diabetes models, a defect in the cyclo-oxygenase pathway is a common observation. Therefore, we hypothesized that the human foetoplacental circulation of diabetic patients is characterized by dysfunction of the cyclo-oxygenase pathway, as well. METHODS: We performed ex-vivo perfusions of isolated placental cotyledons from healthy women (n = 14) and from patients with Type 1 diabetes (n = 9). The contribution of cyclo-oxygenase products to foetoplacental vascular tone was quantified by measuring the response to the cyclo-oxygenase inhibitor indomethacin. RESULTS: Baseline foetoplacental arterial pressure was comparable between controls and diabetic women (mean +/- sem, 21.7 +/- 1.2 vs. 24.4 +/- 2.0 mmHg). Maximum foetoplacental arterial pressure at highest dose of indomethacin was 32.8 +/- 3.0 mmHg in controls vs. 27.3 +/- 2.3 mmHg in diabetic women. The indomethacin-induced increase in pressure was reduced in diabetes (2.9 +/- 0.7 vs. 11.2 +/- 2.4 mmHg in controls, P = 0.01). CONCLUSIONS: Under baseline conditions, the net effect of all cyclo-oxygenase products in the foetoplacental vascular bed is vasodilation. In diabetes, this vasodilator effect seems significantly impaired