Effects of increased neutrophile count on ET1 – induced changes in erythrocyte and leukocyte movements

Abstract

AbstractPurpose It is known that granulocyte‐colony stimulating factor (G‐CSF) increases white blood cell (WBC) count. There is evidence from other vascular beds that an increase in WBC count impairs blood flow regulation in the microcirculation. Whether this also holds true for the ocular circulation is yet unknown. In the following trial we investigated whether an increase in WBC count alters the endothelin‐1 (ET‐1) induced vasoconstriction.Methods 24 healthy male subjects entered this randomized, placebo‐controlled, double masked, two‐way cross over study. 300µg G‐CSF or placebo were applied intravenously to increase WBC count on two study days. Thereafter, ET‐1 (5ng/kg/min) was infused for 30 minutes. Ocular hemodynamic variables were measured before and after G‐CSF treatment and during the last 10 minutes of ET‐1 infusion. Measurements of retinal WBC flux were performed with the blue‐field entoptic technique, blood flow (BF) velocity using a laser Doppler velocimeter and retinal vessel diameter using a Retinal Vessel Analyzer.Results Neither G‐CSF nor ET‐1 had any consistent effect on blood pressure, pulse rate or IOP. G‐CSF induced an increase in retinal WBC density (p<.01). As expected ET‐1 lowered choroidal BF (p<.01), retinal BF (p<.01)and WBC velocity (p=.01). Changes in choroidal BF and WBC velocity in response to ET‐1 were not altered by pre‐treatment with G‐CSF. Contrary, the decrease in retinal BF was more pronounced during leukocytosis (p=.02) as compared to placebo.Conclusion During vasoconstriction, induced by ET‐1, vascular regulation can be altered by the number of circulating leukocytes. Whether this is caused by an interaction of red and white blood cells or by another mechanism is yet unknown.