Inhibition of endothelium-dependent vasorelaxation by sickle erythrocytes.

Abstract

Interactions between erythrocytes and vascular endothelium have been implicated in the pathogenesis of vaso-occlusion in sickle cell anemia. Sickle erythrocytes adhere to endothelial cells and facilitate trapping of rigid sickle cells in microvessels. Compensatory dilation of precapillary arterioles may mitigate the occlusion. The endothelium regulates vasoreactivity by elaborating endothelium-derived relaxing factor (EDRF), a small molecule that passes freely into vascular smooth muscle where it initiates vasorelaxation by activating soluble guanylate cyclase in the smooth muscle cell cytoplasm. Endothelial release of EDRF can be stimulated by agonists such as acetylcholine. It is highly sensitive to decomposition by superoxide anions and is rapidly bound and inactivated by oxyhemoglobin in solution. The purpose of this study was to determine whether sickle cell interaction with endothelium disrupts this mechanism of endothelial regulation of vasomotor tone. Transverse strips of rabbit aorta, mounted isometrically in organ baths, were contracted with norepinephrine, and relaxation responses to acetylcholine or other agonists were determined. Responses were measured under control conditions and again in the presence of oxyhemoglobin A or S, or erythrocytes or ghosts from normal control subjects or patients with homozygous sickle cell anemia. Sickle erythrocytes inhibited vasorelaxation to acetylcholine by 83%. Approximately half of the inhibition was attributable to a small amount of oxyhemoglobin S that was leaked into the buffer from the erythrocytes. Consistent with this, sickle erythrocyte ghosts inhibited vasorelaxation to acetylcholine by up to 45%. Ghosts from normal erythrocytes did not inhibit vasorelaxation to acetylcholine, and the inhibition seen with normal erythrocytes was entirely attributable to leakage of oxyhemoglobin A into the bath buffer.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: M Mosseri, A N Bartlett-Pandite, K Wenc, J M Isner, R Weinstein
• Journal: American heart journal (Am Heart J) Vol. 126 Issue 2 Pg. 338-46 (Aug 1993) ISSN: 0002-8703 [Print] United States
• PMID: 8338004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hemoglobin, Sickle
• Oxyhemoglobins
• Nitric Oxide
• oxyhemoglobin S
• Hemoglobin A
• oxyhemoglobin A
• Superoxide Dismutase
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Anemia, Sickle Cell (etiology, physiopathology)
• Animals
• Endothelium, Vascular (physiology)
• Erythrocyte Membrane (physiology)
• Erythrocytes, Abnormal (physiology)
• Hemoglobin A (pharmacology)
• Hemoglobin, Sickle (pharmacology)
• Humans
• In Vitro Techniques
• Male
• Nitric Oxide (physiology)
• Oxyhemoglobins (pharmacology)
• Rabbits
• Superoxide Dismutase (pharmacology)
• Vasomotor System (drug effects, physiology)