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(-5)M) in the presence or absence of a nitric oxide (NO) synthase inhibitor (L-NNA; 10(-5)M), a cyclooxygenase (COX) inhibitor (indomethacin; 10(-5)M) 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.
Stanley
Joanna L
JL
Maternal & Fetal Health Research Group, University of Manchester, St Mary's Hospital, Whitworth Park, Manchester M13 0JH, UK. jlstanle@ualberta.ca
Ashton
Nick
N
Taggart
Michael J
MJ
Davidge
Sandra T
ST
Baker
Philip N
PN
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000473:pathology / Q000503:physiopathology*; D048909:Diabetes Complications / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D013311:Streptozocin; D014599:Uterus / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013311:Streptozocin; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin