Ilana Ariel1, Galina Skarzinski1, Vitali Belzer2, Wiessam Abu Ahmad3, Zaid Abassi4, Michael Bursztyn5
The Departments of 1Pathology, 2Surgery and 5Medicine, the Hadassah-Hebrew University Medical Center, Mount Scopus, the 3Hebrew University-Hadassah School of Public Health, Ein Kerem, Jerusalem, and the 4Rappaport Faculty of Medicine, Technion, Haifa, Israel
Introduction: Endovascular trophoblasts (EVasT) of the rat express smooth muscle (SM) proteins and contract ex vivo upon exposure to endothelin-1 (ET1) [presented in ISPR 2013]. Contraction is mediated via ET1 receptors A and B (ETA, ETB). In vascular SM ETB, in variance from ETA, exerts also relaxation through activation of nitric oxide synthase (NOS) in the endothelium. Since rat EVasT express NOS we investigated its role in reaction to ET1 exposure.
Material and methods: Cut surface area of modified spiral artery rings devoid of SM was measured ex vivo by addition of L-NAME, a nonspecific inhibitor of NOS, followed by ET1-inducedcontraction, representing the combined contractile effect of both receptors. The same procedure was conducted with ETA antagonist and L-NAME, representing the isolated contractile effect mediated by ETB. Statistical analysis was performed 2-way mixed ANOVA.
Results: L-NAME alone reduced lumen cut surface area by 2.5% (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=0.001. ET1 + ETA inhibitor + L-NAME, representing the isolated constrictive effect of ETB (7.2%), demonstrated earlier and stronger vasoconstriction than via ETA (6.1%) (p< 0.001).
Conclusions: EVasT of the rat remodeled spiral artery react to ET exposure similar to vascular SM of non-modified arteries: contract via receptors A and B and relax via receptor B through NOS activation. We suggest that this phenomenon may play a role in situations of dysregulation of the vasoactive systems.