Abstract

While obesity is a major risk factor for preeclampsia (PE), the mechanisms whereby obesity increases the risk for developing pregnancy-induced hypertension are unclear. Since blood pressure regulation during gestation relies greatly on the nitric oxide (NO) system, we aimed to determine the effects of a HFD on blood pressure and fetal outcomes in pregnant rats treated with NG-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthases. Twelve-week-old Sprague-Dawley female rats were fed a normal diet (ND, 13% fat kcal) or a HFD (40% fat kcal) ad libitum. Body weight (BW) and total fat mass (FM, measured by EchoMRI) were recorded weekly. After 9 weeks of diet treatment, rats were allowed to breed. On gestation day (GD) 14, L-NAME at the concentration 100 mg/L was added to the drinking water of a sub-group of animals (ND + water, n=5; ND + L-NAME, n=6; HFD + water, n=18; HFD + L-NAME, n=16). On GD 19, mean arterial pressure (MAP) was assessed consciously via carotid catheters. Animals were then euthanized and tissues were harvested. Initial BW and FM were similar in ND + water, ND + L-NAME, HFD + water, and HFD + L-NAME (BW: 239.5±4.1 vs. 241.2±4.8 vs. 238.2±2.5 vs. 241.4±2.5 g and FM: 20.4±2.9 vs. 17.9±2.2 vs. 18.2±1.8 vs. 17.4±2.0 g, respectively). By the end of the study, HFD had no effects on BW and FM in pregnant rats (BW: 472.3±5.2 vs. 468.0±10.1 vs. 461.6±12.2 vs. 462.4±8.9 g and FM: 97.5±2.4 vs. 87.3±9.3 vs. 103.3±7.3 vs. 97.5±6.0 g, respectively). Although MAP was elevated in L-NAME treated pregnant rats, HFD did not alter MAP or exacerbate the effect of L-NAME on MAP (106.6±5.0 vs. 131.3±4.9 vs. 116.0±2.7 vs. 130.2±2.8 mmHg, respectively; P<0.05). Neither HFD nor L-NAME affected litter size (13.0±0.8 vs. 13.2±1.2 vs. 12.0±1.0 vs. 12.1±0.8 number of fetuses per rat, respectively). However, HFD reduced fetal weight equally in water and L-NAME treated pregnant rats (2.2±0.0 vs. 2.2±0.1 vs. 2.1±0.0 vs. 2.0±0.0 g, respectively; P<0.05). In summary, while HFD had a detrimental effect on fetal weight, it had no effect on blood pressure regulation during pregnancy.

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