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J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:p> The effects of endothelin-1 (ET-1) on erythrocytes from sickle cell disease (SCD) patients have been described, but mechanisms of ET-1 regarding primary erythrocyte functions remain unknown. ET-1 is a vasoconstrictor peptide produced by endothelial cells, and the expression of ET-1 is increased in SCD. The present study used ex vivo experiments with sickle cell erythrocytes, ET-1, and bosentan, a dual antagonist of ET<jats:sub>A<\/jats:sub> and ET<jats:sub>B<\/jats:sub> receptors. We performed a hemoglobin S (HbS) polymerization assay with three concentrations of ET-1 (1, 20, and 50 pg\/mL) and bosentan (100\u00a0nmol\/L). ET-1 increased HbS polymerization at all concentrations, and this effect was suppressed by bosentan. For the deformability assay, red blood cells (RBCs) were incubated on a Sephacryl column with the same concentrations of ET-1 and bosentan. ET-1 decreased deformability, and this effect was reversed by bosentan. To observe erythrocyte adhesion, ET-1 and bosentan were incubated with RBCs in thrombospondin-coated 96-well plate, which demonstrated that ET-1 decreased adhesion but that bosentan enhanced adhesion. We also assessed erythrocyte apoptosis and observed decreased eryptosis induced by ET-1, and these effects were inhibited bosentan. Thus, these findings demonstrated that ET-1 modulates HbS polymerization, erythrocyte deformability, adhesion to thrombospondin, and eryptosis, and these effects were suppressed or enhanced by bosentan. <\/jats:p>","DOI":"10.1139\/cjpp-2022-0012","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T21:33:20Z","timestamp":1677188000000},"page":"642-651","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bosentan attenuates sickle cell disease erythrocyte HbS polymerization and impaired deformability induced by endothelin-1"],"prefix":"10.1139","volume":"101","author":[{"given":"Lyzes","family":"Rosa Teixeira-Alves","sequence":"first","affiliation":[{"name":"Grupo de Pesquisa em Fisiologia Eritr\u00f3ide-GPFisEri, Universidade Federal do Rio de Janeiro","place":["Campus Maca\u00e9, Brazil"]},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Endocrinologia, Faculdade de Medicina, 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