OBJECTIVE: The onset of maternal hypertension is a hallmark feature of preeclampsia, resulting from widespread endothelial dysfunction and systemic vasoconstriction. Central to this study, we set out to create a new model that mimics the vascular dysfunction in preeclampsia to evaluate new therapeutic strategies.
METHODS: Human omental arteries were collected from normotensive pregnant women at term (n=9). Serum was collected from women with pregnancies complicated by preterm preeclampsia (delivery <34 weeks gestation, n=8), term preeclampsia (delivery >37 weeks gestation, n=5) and healthy gestation matched controls (n=15). We performed ex vivo whole vessel wire myography (DMT 620M) to investigate the vascular effects of treatment with serum from these pregnancies. Omental vessels were treated with increasing doses of serum (2-20%) to assess vasoconstriction. Vessels pre-constricted with preterm serum were then treated with esomeprazole (0.1-100uM), a candidate therapeutic for preeclampsia.
RESULTS: All vessels constricted in response to pregnant serum. There was no significant difference in constriction between human omental arteries in response to either preterm or term preeclamptic serum, compared to gestation matched controls. Esomeprazole treatment did not alter omental artery vasorelaxation in response to normotensive serum. However, esomeprazole treatment significantly enhanced vasorelaxation of arteries pre-constricted with preterm preeclamptic serum compared to vehicle control.
CONCLUSION: Here we developed sophisticated human physiological models of preeclamptic vascular constriction to better test therapeutic strategies. These data demonstrate the exciting potential of our new models; esomeprazole, a novel therapeutic candidate, directly enhances vascular relaxation following constriction driven by serum derived preeclamptic mediators.