Acute hyperglycemia in uterine arteries from pregnant, but not non-pregnant mice, enhances endothelium-dependent relaxation.
Poorly controlled diabetes in pregnancy, characterized by hypo- and hyperglycemia, is associated with adverse outcomes. We hypothesized that aberrant glucose levels affect vascular function in pregnancy. The effects of glucose concentration on constriction and endothelium-dependent relaxation in uterine arteries of normal C57BL/6 mice were examined. Ex-vivo arteries from 18 pregnant and 14 non-pregnant mice were mounted on a wire myograph, constricted with phenylephrine and relaxed with incremental doses of acetylcholine, in physiological saline solution containing 5 mmol/L glucose. Arteries were then exposed to solutions with 2, 5, 8 or 12 mmol/L glucose for 30 min and constriction/relaxation repeated. On altering glucose concentrations to 2, 8 or 12 mmol/L, maximal constriction was increased in arteries from pregnant but not from non-pregnant mice (paired t-test, p<0.05). Endothelium-dependent relaxation was enhanced at 12 mmol/L glucose in arteries from pregnant (two-way ANOVA, p<0.01), but not from non-pregnant mice. Endothelium-dependent relaxation in the uterine artery was pre-dominantly mediated by a non-nitric oxide/non-prostanoid mechanism, with a smaller contribution from nitric oxide, and no prostanoid-mediated relaxation. In summary, acute changes in glucose concentration alter both constriction and endothelium-dependent relaxation in uterine arteries of normal pregnant mice; these effects are unique to pregnancy.
Chirayath
Haiju H
HH
Maternal and Fetal Health Research Centre, The University of Manchester, St. Mary's Hospital, M13 0JH, United Kingdom. haiju.chirayath@gmail.com
Wareing
Mark
M
Taggart
Michael J
MJ
Baker
Philip N
PN
D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D005947:Glucose; D000109:Acetylcholine