Chorionic plate arterial function is altered in maternal obesity

Abstract

Objectives: To characterise Chorionic Plate Artery (CPA) function in maternal obesity, and investigate whether leptin exposure reproduces the obese CPA phenotype in normal-BMI women.

Study design: CPA responses to the thromboxane-A(2) mimetic U46619 (pre/post leptin incubation), to the nitric oxide donor sodium nitroprusside (SNP) and the occurrence of tone oscillations (pre/post leptin incubation) were assessed in 46 term placentas from women of normal (18.5-24.9) or obese (>30) Body Mass Index (BMI).

Outcome measures: Area Under the dose response Curve (AUC), maximum response (V(max)), sensitivity (EC(50)) to U46619 (pre/post leptin) and SNP; average vessel tone, oscillation amplitude and frequency (pre/post leptin).

Results: U46619 vasoconstriction was similar between BMI categories (p > 0.05), however vasodilatation to SNP was reduced in obesity (AUC p = 0.02, V(max)p = 0.04) compared to normal-BMI women. Leptin incubation altered responses to U46619 in both normal-BMI (EC(50) at 100 ng/ml leptin; p < 0.05) and obese women (AUC at 50 ng/ml; p < 0.05) but vasomotion was unaffected (p > 0.05).

Conclusions: Maternal obesity is associated with altered placental vascular function which may adversely affect placental oxygen and nutrient transport, placing the fetus at risk. Leptin incubation altered CPA vascular function but did not reproduce the obese phenotype.

Fig. 1

Study protocol.

Fig. 2

Examples of original tracings illustrating U46619-induced tone oscillations with 1 μM bradykinin (BK) added at the end of the exposure period. The peak constriction (PC) and average tone over the last 15 min of the U46619 constriction were calculated for each CPA. Oscillations during the U46619 constriction were defined as a change in tone (peak to trough) of >10% compared to the PC. Mean amplitude (OA) and frequency (min⁻¹) of oscillations to U46619 were calculated for each artery. The maximum response, average tone, oscillation amplitude and frequency over 15 min were calculated for BK exposure.

Fig. 3

Effect of maternal BMI on chorionic plate artery vasoconstriction. Vasoconstriction response of CPAs to the thromboxane-A2 mimetic U46619 was unaltered between BMI cohorts: a) Dose response curves; Area under the curve (AUC; p > 0.05). b) Maximal response (V_max; p > 0.05). c) Sensitivity (EC₅₀; p > 0.05).

Fig. 4

Effect of maternal obesity on chorionic plate artery vasodilation. Vasodilation response of CPAs to the nitric oxide donor sodium nitroprusside is impaired by maternal obesity: a) Dose response curve (AUC; p = 0.02). b) Maximal response (V_max; p = 0.04).