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

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 37oC 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.