In vitro effects of norepinephrine (NE) and isoprenaline (IP) on erythrocyte rheology under normal and pathologic conditions

Abstract

Although previous reports have indicated that catecholamines can produce changes in RBC flow behavior, RBC microrheologic studies with these agents appear to be limited. The present study was therefore designed to evaluate the effects of both an alpha-stimulator norepinephrine (NE) and a beta-stimulator isoprenaline (IP) on RBC deformation in defined shear fields as well as on RBC filterability under pathologic conditions. Various concentrations of NE and IP (10-4M - 10-9M) were added to fresh human RBC suspended in isotonic phosphate or HEPES buffered saline at physiologic pH and the cells incubated for 30 min at room temperature. RBC deformation measurements were carried out in a counter-rotating rheoscope over a shear stress range of .25 – 50 Pa. RBC filterability (5 µm pores, 10% Hct) was investigated at physiologic pH and under pathologic conditions using the following stress models: a) pH = 7.0; b) increased external calcium concentration (pH = 7.4, 9 mM Ca); c) 9mM Ca plus ATP depletion via 2-deoxyglucose. In the rheoscope, RBC incubated with 10-5M NE showed a decrease in cell deformation at low shear stresses and a decrease over the entire shear stress range was found after incubation with 10-4 M NE. IP at 10-4 and 10-5 M did not alter cell deformation at pH = 7.4, whereas lower IP concentrations (10-7 M and 10-9 M) lead to an increase in cell deformation at the lowest shear stresses. Compared to the filterability of controls at pH 7.4, RBC filterability was decreased in all stress situations. Increasing NE concentrations significantly worsened the reduction in cell filterability in the stress models, while the effects of IP were more variable: with IP, either there was no change in filterability or small but significant increases. Our results suggest that NE, an alpha-receptor agonist, may negatively alter RBC flow properties in regions of high NE concentrations (i.e. local areas of infarcted myocardium), whereas beta-receptor-agonists, such as IP, could be beneficial to blood flow in low concentrations.