Abstract P095: Effects of Obesity on Placental Ischemia-induced Hypertension
Although it is known that obesity is a risk factor for preeclampsia (PE), the mechanisms are not clear. Placental ischemia stimulates the release of the antiangiogenic factor sFlt-1 into the maternal circulation eliciting vascular dysfunction and hypertension. Therefore, we tested the hypothesis that placental ischemia (reduced uterine perfusion pressure, RUPP)-induced hypertension and sFlt-1 levels are exaggerated in obese rats. MC4R-deficient obese rats (MC4R+/-) and wild-type Wistar Hannover controls (MC4R+/+) were maintained on NIH31 standard chow; mated at 17 weeks old; RUPP surgeries performed at gestational day (GD) 14; and mean arterial blood pressure (MAP) and pregnancy weights assessed at GD 19. This resulted in 4 groups: normal pregnant (NP) MC4R+/+ (N=10), RUPP MC4R+/+ (N=12), NP MC4R+/- (N=12) and RUPP MC4R+/- (N=11). Body weight was greater in NP MC4R+/- than NP MC4R+/+ (371±10 vs. 340±6, P<0.05), which was reduced by RUPP in both rat strains but MC4R+/- were still heavier (327±13 vs. 297±8, P<0.05). Total body fat mass by EchoMRI was greater in NP MC4R+/- than MC4R+/+ (72±6 vs. 45±4, P<0.05) whereas fat mass was not altered in RUPP MC4R+/+ (38±4g) but was reduced in RUPP MC4R+/- (56±5) (P<0.05). Fetal weights were similar between NP MC4R+/+ (1.93±0.04) and MC4R+/- (1.95±0.02), which was reduced to a greater extent in RUPP MC4R+/- than MC4R+/+ (1.62±0.03 vs. 1.74±0.03, P<0.05). MAP was slightly elevated in NP MC4R+/- over MC4R+/+ (107±2 vs. 101±1). RUPP significantly increased MAP in MC4R+/+ (117±2, P<0.05) but not MC4R+/- (113±3). Plasma leptin levels were greater in NP MC4R+/- over MC4R+/- (6.7±1.0 vs. 3.6±0.4, P<0.05) whereas RUPP had no effect on these levels in MC4R+/+ (3.8±0.7) or MC4R+/- (6.5±1.1). Plasma and placental levels of sFlt-1 were similar in all groups. Clinically, not all PE women have elevated sFlt-1 levels. Contrary to our hypothesis, MAP was not exaggerated by placental ischemia in obese rats having MC4R deficiency. In fact, MAP was not significantly increased following placental ischemia in MC4R-deficient rats indicating that intact MC4R signaling, which has been shown to promote the development of hypertension in several animal models by sympathetic mechanisms, mediates the development of PE independent of sFlt-1.
Author Disclosures: F.T. Spradley: None. A.C. Palei: None. J.P. Granger: None.
- © 2015 by American Heart Association, Inc.