Influence of haemoglobin solution from sickled erythrocytes on endothelium-dependent relaxation of isolated rabbit carotid arteries

Abstract

There are conflicting reports concerning vascular reactivity changes in sickle cell anaemia (SCA). The goal of the present study was to examine possible interactions between components of sickle erythrocytes and the vascular endothelium, that may alter vascular reactivity in isolated rabbit carotid arteries. Endothelium-dependent acetylcholine (Ach)-induced relaxation responses (following phenylephrine pre-contractions) were examined in control rabbit carotid artery rings as well as in rings exposed for 30 min to various erythrocyte components obtained from subjects of different Haemoglobin (Hb) genotypes (AA, AS and SS), under standard organ bath conditions: 2 mm rings suspended in 20ml organ baths containing physiological salt solution (PSS) bubbled with 95% O₂, 5% CO₂, at 37^oC and pH 7.4 and isometric contractions measured, under an initial load of 2g. Arterial rings were exposed to 50μl of each of the erythrocyte constituents at an adjusted haematocrit of 0.6. Intact Erythrocytes of Hb AA and SS had no effect on Ach relaxation while AS erythrocytes caused a significant inhibition (P<0.05) by 25%. Exposure to Hb solutions from Hb AA and AS subjects had no inhibitory effect on Ach relaxation whereas a 30% inhibition occurred in Hb SS. Erythrocyte ghosts produced no inhibition with Hb AA, AS and SS. We propose that the haemoglobin content of Hb SS appears likely to be associated with an enhanced inhibition of endothelial function in Hb SS subjects and may predispose more cardiovascular complications especially during haemolytic crisis in SCA.

Keywords: Vasorelaxation, EDRF, sickle cell anaemia, endothelium, haemoglobin solutions, haemoglobin genoytpes