Impact of experimental diabetes on the maternal uterine vascular remodeling during rat pregnancy

Abstract

Normal pregnancy is associated with an increase in uteroplacental blood flow in part due to growth and remodeling of the maternal uterine vasculature. In this study, we characterized the effect of diabetic pregnancy on vascular growth of the maternal uterine vasculature and on the passive mechanical properties of the uterine resistance arteries. Diabetes was induced in pregnant rats by injection of streptozotocin and confirmed by development of hyperglycemia. Fetuses of diabetic rats were significantly smaller and placentas larger compared to controls. Pregnancy-induced axial elongation of the mesometrial uterine vasculature was not altered by diabetes. Vascular wall thickness was unchanged between groups. Wall distensibility was increased and the rate constant of an exponential function fitted to stress-strain curve was significantly reduced demonstrating decreased wall stiffness in diabetic uterine radial arteries compared to controls. We conclude that experimental diabetes in rat pregnancy does not compromise the growth of maternal uterine vasculature but alters passive mechanical properties of the uterine radial arteries.

Figure 1

Marked elevation in average blood glucose levels in rats after intraperitoneal injection of streptozotocin (STZ) throughout pregnancy. Citrate buffer-injected animals maintained euglycemia. Note: Error bars are smaller than the size of the symbols.

Figure 2

A, A photograph of a uterine horn and mesometrial uterine vasculature from a 20-day control pregnant rat.; A—the distance from MUA to uterine wall; B—the distance from MUA to the placenta. B, A photograph of the enlarged section of mesometrial vasculature showing anatomical location of uteroplacental (a) and premyometrial (b) radial arteries used in the current study. Arcuate (c) and main uterine (d) arteries are shown as well. MUA indicates main uterine artery.

Figure 3

Bar graphs demonstrating no significant changes in wall thickness (A) and lumen diameter (B) of main uterine artery from diabetic (STZ) compared to control (Citrate) 20-day pregnant rats. All measurements were performed from vessels in the presence of 50 µmol/L papaverine and 20 µmol/L diltiazem at the levels of intralumenal pressure of 5, 50, and 80 mm Hg.

Figure 4

Experimental diabetes during pregnancy did not alter wall thickness of uteroplacental (A) and premyometrial (B) radial arteries at intralumenal pressures of 5, 50, and 80 mm Hg. All measurements were performed from vessels in the presence of 50 µmol/L papaverine and 20 µmol/L diltiazem.

Figure 5

Effect of experimental diabetes on passive lumen diameters of uteroplacental (A) and premyometrial (B) radial arteries plotted as a function of intralumenal pressure. *Significantly different at P < .05 (2-way repeated measures analysis of variance).

Figure 6

Effect of experimental diabetes on wall distensibility of the main uterine artery (A), uteroplacental (B) and premyometrial (C) radial arteries. Distensibility is expressed as percentage of pressure-induced changes in lumen diameter relative to that of an unstretched artery at minimal intralumenal pressure of 3(5) mm Hg. *Significantly different between control (citrate) and diabetic (STZ) rats at P < .05 (2-way repeated measures analysis of variance).

Figure 7

Circumferential stress–strain relations and the rate constants (stiffness coefficient β) in the main uterine artery (A and B), uteroplacental radial arteries(C and D) and premyometrial arteries (E and F) of control (citrate) and diabetic (STZ) 20-day pregnant rats.*Significantly different between control (citrate) and diabetic (STZ) rats at P < .05 (unpaired Student t test).