263: In vitro uterine artery reactivity in a pregnant mouse model of preeclampsia induced by over-expression of sFlt-1


      We have previously validated a mouse model of preeclampsia induced by adenovirus-mediated over-expression of sFlt-1. Our objective was to further investigate the underlying mechanisms for the preeclampsia-like condition in this animal model by evaluating the vascular reactivity of the uterine artery.

      Study Design

      At day 8 of gestation, CD-1 mice were randomly allocated to injection of the adenovirus carrying Flt (1-3) [AdFlt(1-3); 109 PFU] or adenovirus carrying mFc control (109 PFU) via the tail vein (n=6/group). At day 18 of gestation, the mice were sacrificed and 2 mm segments of uterine artery were mounted in a wire myograph for isometric tension recording. Contractile responses to phenylephrine (PE, 10-10 - 10-5 M) were assessed in the presence and absence of L-NAME, an inhibitor of nitric oxide synthase. In addition, concentration-response curves to the endothelium-dependent relaxing agent acetylcholine (Ach, 10-10 - 10-5 M), the endothelium-independent relaxing agent sodium nitroprusside (SNP, 10-10 - 10-5 M), and thromboxane A2 (TxA2, 10-10 - 10-6 M) were obtained. Student t test was used for statistical analysis (significance: p<0.05).


      The maximal response to PE in the sFlt-1 group was significantly higher compared with control (187.98 ± 15.13 vs 118.70 ± 9.29 %, P=0.008), but this difference was abolished in the presence of L-NAME. The relaxation to Ach was significantly decreased in the sFlt-1 group compared with control (28.27±12.3 vs 86.79±4.86 %, P=0.007). No differences were noted in the SNP and TXA2 responses.


      The previously characterized preeclampsia-like condition induced by over-expression of sFlt-1 is accompanied by impaired uterine vascular reactivity, likely due to endothelial dysfunction. We speculate that this altered vascular function leads to impaired placenta perfusion and preeclampsia. Further investigations focusing on the uterine vasculature and the underlying pathologic mechanisms in this animal model are warranted.