P4.16 THE MYOTROPHOBLAST OF THE RAT PLACENTA: EX VIVO STUDY OF NITRIC OXIDE SYNTHASE INHIBITION

Abstract

Introduction: Endovascular trophoblasts (EVasT) of the rat express smooth muscle (SM) proteins and contract ex vivo upon exposure to endothelin-1 (ET1). Contraction is mediated via ET1 receptors A and B (ETA, ETB). In vascular SM ETB, in variance from ETA, exerts relaxation through activation of nitric oxide synthase (NOS). We investigated the role of NOS expressed by EVasT in reaction to ET1 exposure. M&M: Cut surface area of remodeled spiral artery rings devoid of SM was measured ex vivo exposed to (a) L-NAME alone, (b) L-NAME and ET1 representing the combined contractile effect of both receptors, and (c) L-NAME with ET1 and ETA antagonist, representing the isolated contractile effect mediated by ETB. These curves were compared with ET1-induced contraction in the presence of receptor antagonists without L-NAME. Statistical analysis was performed 2-way mixed ANOVA. Results: L-NAME alone reduced lumen cut surface area by 2.2±0.3.% (p=0.002). ET1+L-NAME, representing the sum of constrictive effect via ETA and ETB reduced vascular lumen area immediately, compared with a plateau at 60min by addition of ET1 alone, p=0.004. ET1 + ETA inhibitor + L-NAME, representing the isolated constrictive effect of ETB (5.9±0.6%), demonstrated similar vasoconstriction via ETA (5.3±0.5%) (p=0.018). Conclusions: EVasT of the rat remodeled spiral artery react to ET1 exposure similar to vascular SM of non-modified arteries: contract via ETA and ETB and relax via ETB through NOS activation. This phenomenon may play a role in situations of dysregulation of the vasoactive systems in rat models of preeclampsia and IUGR.