Vasoactive factors in sickle cell disease: In vitro evidence for endothelin-1-mediated vasoconstriction

Sitki Ergul, Chris Y. Brunson, Jim Hutchinson, Amany Mohamed Tawfik, Abdullah Kutlar, R Clinton Webb, Adviye Ergul

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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 ETA 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.

Original languageEnglish (US)
Pages (from-to)245-251
Number of pages7
JournalAmerican Journal of Hematology
Volume76
Issue number3
DOIs
StatePublished - Jul 1 2004

Fingerprint

Sickle Cell Anemia
Endothelin-1
Vasoconstriction
Hemoglobins
Blood Vessels
Endothelial Cells
Erythrocytes
Conditioned Culture Medium
In Vitro Techniques
Pulmonary Artery
Cultured Cells
Control Groups

Keywords

  • Endothelin-1
  • Sickle cell disease
  • Vasoactive factors
  • Vasoconstriction

ASJC Scopus subject areas

  • Hematology

Cite this

Vasoactive factors in sickle cell disease : In vitro evidence for endothelin-1-mediated vasoconstriction. / Ergul, Sitki; Brunson, Chris Y.; Hutchinson, Jim; Tawfik, Amany Mohamed; Kutlar, Abdullah; Webb, R Clinton; Ergul, Adviye.

In: American Journal of Hematology, Vol. 76, No. 3, 01.07.2004, p. 245-251.

Research output: Contribution to journalArticle

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