Sickle erythrocytes enhance phenylephrine and histamine contractions of isolated rabbit carotid arteries
The mechanisms of altered vascular reactivity induced by sickle erythrocyte-endothelium interaction remain unclear. The goal of the present study was to examine, comparatively the influence of sickle erythrocyte on contractile responses induced by phenylephrine and histamine. Concentration-dependent contractile responses 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, as described previously: 2 mm arterial rings preparations were placed 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 equilibrated for 60 minutes and then exposed to 50µl of each of the erythrocyte constituents at an adjusted haematocrit of 0.6. The respective EC50 (M) values for phenylephrine (PE) and histamine (H) contractions in control carotid arterial rings were 5.1 (±1.4) x10-6 (n=7) and 6.3± (1.7) x10-5 (n=11). PE contractions were uninfluenced by Hb SS RBCs but significantly enhanced by RBCs from Hb AA and AS subjects: EC50 (M) = 7.3 (±6.6) x10-7, n=6 and 2.5 (±2.3) x 10-6, n=6 respectively. H contractions were significantly enhanced by only RBCs from Hb AS and SS subjects: EC50 values for H is 4.1 (±2.0) x 10-5, n=6 and 4.6 (± 2.1) x 10-5, n=7 respectively. The EC50 ratios for PE contractions following exposure to erythrocytes from Hb AA and AS subjects (6.94 and 2.032) respectively are greater than for H contractions following exposure to erythrocytes from Hb AA, AS subjects (0.971, 1.563) respectively, P<0.05. These ratios show greater enhancement of PE contractions in the order AA RBC > AS RBC. SS RBC did not significantly alter PE contractions but significantly enhanced H contractions. The greater RBC-induced enhancement of histamine contractions, compared with phenylephrine (in AS and SS), suggests a possible role for histamine in the increased vascular tone and vaso-occlusive crisis in sickle cell disease.