Dysfunction of the cyclo-oxygenase pathway in the foetoplacental circulation in Type 1 diabetes mellitus.
OBJECTIVE
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.
Bisseling
T M
TM
Department of Pharmacology-Toxicology, University Medical Cenger, Nijmegen, the Netherlands.
Wouterse
A C
AC
Steegers
E A P
EA
Elving
L
L
Russel
F G M
FG
Smits
P
P
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin; D021041:Placental Circulation / Q000187:drug effects; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000201:enzymology* / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin