Uterine artery function in a mouse model of pregnancy complicated by diabetes

It has been demonstrated previously that endothelium-dependent vasodilatation is impaired in myometrial arteries from women with gestational diabetes, which may play a role in mediating complications observed in diabetic pregnancies. It is not known which aspects of endothelium-dependent vasodilatation are impaired, thus a mouse model of pregnancy complicated by streptozotocin-induced diabetes was established to investigate underlying mechanisms. Uterine arteries from term-pregnant, diabetic and control C57Bl6/J mice were assessed using acetylcholine (ACh; 10− 10–10− 5M) in the presence or absence of a nitric oxide (NO) synthase inhibitor (L-NNA; 10− 5M), a cyclooxygenase (COX) inhibitor (indomethacin; 10− 5M) or the two in combination. Sensitivity to ACh was comparable between diabetic and control mice. However, the contribution of endothelium-dependent vasodilators was significantly altered. L-NNA significantly inhibited the relaxation of arteries from diabetic compared to control mice (65 ± 11% vs 18 ± 6%; p < .05). L-NNA and indomethacin significantly inhibited the relaxation of arteries from diabetic mice compared to control (87 ± 5% vs 33 ± 14%; p < 0.05). These data indicate that endothelium-dependent relaxation of the uterine artery of control, pregnant mice was largely mediated by the non-NO/non-COX component. Surprisingly, arteries from diabetic mice were primarily dependent on NO, which may affect compensatory capacity as the disease progresses.