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Vasoactive factors in sickle cell disease: In vitro evidence for endothelin‐1‐mediated vasoconstriction
Author(s) -
Ergul Sitki,
Brunson Chris Y.,
Hutchinson Jim,
Tawfik Amany,
Kutlar Abdullah,
Webb R. Clinton,
Ergul Adviye
Publication year - 2004
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20107
Subject(s) - vasoconstriction , vasoactive , endothelin receptor , medicine , in vitro , endothelin 1 , disease , immunology , biology , receptor , genetics
While systemic plasma endothelin‐1 (ET‐1) levels are increased during acute crisis in sickle cell disease, the relative levels of potent vasoactive factors that contribute to the regulation of vascular function, such as ET‐1, NO, and cell‐free hemoglobin, during the course of periodic vaso‐occlusive episodes remain unclear. Moreover, whether and to what extent sickling‐induced release of ET‐1 alters vascular tone is not completely understood. To investigate the sequential changes in circulating vasoactive factors, we measured plasma ET‐1, NO metabolites (NOx), and cell‐free hemoglobin (Hb) before (steady‐state), during (crisis), and after a vaso‐occlusive (post‐crisis) episode. Steady‐state ET‐1 levels (fmol/mL) increased from 2.3 ± 0.4 to 11.0 ± 1.4 and 4.2 ± 1.0 during crisis and post‐crisis periods, respectively. There was no significant difference in plasma NOx levels. Cell‐free Hb levels were significantly higher in sickle cell patients in all phases as compared to the control group, and especially during crisis cell‐free Hb levels were elevated by 4‐fold (209,000 ± 31,000 vs. 46,000 ± 5,300 ng/mL in steady‐state). Conditioned medium from human pulmonary artery endothelial cells exposed to sickled erythrocytes prepared by deoxygenation induced contraction of aortic rings, and this effect was blocked by an ET A receptor antagonist. These findings indicate that ET‐1 is the predominant contractile factor released by cultured endothelial cells upon exposure to deoxygenated sickled SS erythrocytes and ET‐1–NO–NO scavenger balance is altered in favor of vasoconstriction during an acute episode in SCD. Am. J. Hematol. 76:245–251, 2004. © 2004 Wiley‐Liss, Inc.