Hawthorn special extract WS ® 1442 increases red blood cell NO-formation without altering red blood cell deformability

Abstract

WS ® 1442 is a special extract of hawthorn leaves with flowers used for the treatment of mild cardiac failure. The activation of endothelial nitric oxide synthase (eNOS) has been shown to contribute to its vasodilating properties. Quite recently it has been demonstrated that red blood cells (RBCs) express a functional NO-synthase (rbcNOS) and rbcNOS activation has been associated with increased RBC deformability. The aim of the present study was to determine whether WS ® 1442 is able to activate rbcNOS, to induce NO-formation in RBC and to alter RBC-deformability. Blood from healthy volunteers was incubated with WS ® 1442 (25–100 μg/ml) for up to 30 min. RbcNOS activation was detected by immunohistochemical staining of phosphorylated rbcNOS and NO-formation was examined by diaminofluorescein (DAF) fluorescence. RBC deformability was measured by a laser assisted optical rotational cell analyzer. Serine 1177 of RbcNOS (rbcNOS Ser 1177) was time- and concentration-dependently phosphorylated by WS ® 1442. Rates of rbcNOS Ser 1177 phosphorylation were up to 149% higher in RBCs treated with WS ® 1442 in comparison to control (DMSO 0.05%). WS ® 1442 induced a time-dependent increase in NO-formation in RBCs which reached its maximum after 5 min. An increase in shear stress (0.3–50 Pa) caused an increase in RBC deformability. WS ® 1442 did not change either basal or maximal RBC-deformability or shear stress sensitivity of RBC at normoxia. Conclusion WS ® 1442 activates rbcNOS and causes NO-formation in RBCs. WS ® 1442-dependent NO-formation however does not affect RBC-deformability at normoxia.