Acute intravenous administration of Resveratrol significantly increases maternal uterine artery blood flow in a nonhuman primate model

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 708-722-Obesity: Response to Interventions
Basic
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-722
Victoria HJ Roberts*1, Jessica L Walker1, Kevin L Grove1, Kent L Thornburg2 and Antonio E Frias Jr.3
1Oregon Health and Science University/ONPRC, Beaverton, OR, 2Oregon Hlth Sci Univ, Portland, OR, 3Oregon Health and Science University, Portland, OR
Adequate uterine blood flow is essential for normal placental development and fetal growth. We have previously demonstrated by Doppler ultrasound (US) that consumption of a high fat diet (HFD, 36% fat calories) during pregnancy results in a reduction in uteroplacental perfusion in our nonhuman primate (NHP) model. The dietary supplement, Resveratrol (Resv) has been demonstrated as an endothelium vasodilator in addition to its actions as a calorie restriction mimetic. The objective of this study was to examine the acute effects of intravenous (IV) administration of Resv on maternal uterine artery blood flow (Quta) in our NHP model. Pregnant Japanese Macaques (n=3) maintained on a HFD underwent IV Resv infusion with US at 120 days of gestation (term = 175 days) with C-section delivery and placental collection at 130 days. For Resv infusion, animals were maintained under sedation with isofluorane and received continuous IV infusion of Lactated Ringers (5ml/kg/hr) with 5ml boluses of 0.7% ethanol vehicle, 0.2mg Resv, 0.5mg Resv and 1.0mg Resv respectively at 30 minute intervals for 2 hours in total. Maternal plasma was collected at 30 minute intervals and assayed for Resv content. One additional animal underwent IV infusion at 5ml/kg/hr with 5ml saline boluses as a control for potential effects of increased blood volume on uteroplacental blood flow. UTA diameter, velocity time interval (VTI) and fetal heart rate (FHR) were measured at 5 min intervals throughout (Quta = VTI x FHR x cross sectional area).  By US, we observed a dramatic increase in UTA vessel diameter and VTI which resulted in a 2.5-fold increase in Quta following Resv infusion (Baseline: 14.82 ± 4.13ml/min/kg, Peak: 39.47 ± 4.18ml/min/kg, mean ± SD, p<0.05 paired t-test, n=3). There was no effect of either vehicle infusion (n=3) or control fluid infusion (n=1) on Quta which increased in a dose-dependent manner with Resv. Maternal plasma Resv content increased from baseline levels of 0.18 ± 0.09ng/ml to 3.68 ± 1.74ng/ml (mean ± SD) following infusion of the maximal dose of 1.0mg Resv. This acute in vivo study in a relevant animal model demonstrates a potent and direct vasodilatory effect of Resv on the maternal uterine artery which may have translational value when vascular insufficiency is detected by US in pregnant women. If Resveratrol proves safe for fetal development, it may be a suitable intervention to improve placental function and fetal outcome when uterine blood flow is deficient.

Nothing to Disclose: VHR, JLW, KLG, KLT, AEF Jr.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH/NIDDK grant R24 DK090964 awarded to KG and KT. P51 OD011092 (KT and AF).
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