Dihydroergocryptine maintains erythrocyte fluidity in acidotic and hyperosmolar buffer solutions modelling hypoxic and ischemic microcirculation

Abstract

Received 20,09.1994; accepted 21.12.1994) The positive effects of Ergopeptide Alkaloids, particularly Dihydroergotoxine with Dihydroergocryptine (DHEC) as one of the components, on cerebral functions has been known for about three decades. DHEC in particular has multiple biological effects: It is an a-ad reno receptor blocking agent and an agonist of dopamine receptors and is known as a peripheral and cerebral vasodilator. An anti-aggregative activity has been shown on platelet aggregation induced by adrenaline and collagen as well as on erythrocyte aggregation induced by dextran. It also is a metabolic enhancer, protecting against metabolic stress due to hypoxia and ischemia and it increases the uptake of deoxyglucose and oxygen utilisation in the brain. We studied the protective effect of DHEC (concentration range 10 nM to 100 /lM) on human red blood cell (RBC) rheology in acidotic and hyperosmolar solutions (AHS) modelling the hypoxic and ischemic microcirculation. The microscopic photometric monolayer technique was used to quantify alterations of RBC resting shape, stiffness and relaxation time automatically and time dependently (Elias-c-analyser). The technique is based on changes in light transmission through a RBC monolayer in a flow chamber at controlled shear stresses. A HEPES buffer solution was used as control buffer and an acidotic/hyperosmotic buffer solution (pH 6.8, 380 mosmoVkg) to simulate the metabolic challenge in ischemia. AHS itself hardly altered the RBC discocytic shape. However, it significantly increased RBC stiffness and relaxation time (p<O.OOI). Both RBC in control buffer and RBC pre-stressed in AHS for 20 minutes were incubated with DHEC at different concentrations within the flow chamber. DHEC-induced stomatocytes appeared dose-dependently in both, control buffer and AHS, within less than 2 minutes. The shape change was 1