Effects of nitric oxide and prostacyclin on deformability and aggregability of red blood cells of rats ex vivo and in vitro

Abstract

Although many diseases of the heart and circulatory system have been linked with insufficient deformability and increased aggregability of red blood cells, there are only a few drugs which can modulate these biological functions of erythrocytes. Here, we show evidences that iloprost, stable prostacyclin analogue and SIN-1, active metabolite of molsidomine which spontaneously releases NO, may be sufficient pharmacological tools for modulating red blood cell deformability and aggregability. Deformability of red blood cells was measured by shear stress laser diffractometer (Rheodyn SSD) and expressed in percent of red blood cell deformability index (DI). MA-1 (Myrenne) erythrocyte aggregometer was used for photometric measurements of aggregability in arbitrary units (MEA) of mean extent of aggregation. Experiments were carried out on rats ex vivo and in vitro using whole rat blood or isolated erythrocytes. Ex vivo SIN-1 (infusion 2 mg/kg/min i.v.) and iloprost (bolus injection 10 microg/kg i.v.) significantly improved erythrocyte deformability and aggregability at 5-15 min after administration. L-NAME (10 mg/kg i.v.)- inhibitor of nitric oxide synthase, and aspirin (1 mg/kg i.v.) caused worsening of deformability of erythrocytes in experiments ex vivo. Studies in vitro also revealed improvement of red blood cell deformability and aggregability by SIN-1 (3 microM, 15 min incubation at 22 degrees C) or iloprost (1 microM, 15 min incubation at 22 degrees C) and this phenomenon appeared not only in whole blood but also in isolated red cells. It is concluded that NO- and prostacyclin-induced improvement of red blood cell deformability and aggregability results from direct action of these compounds on erythrocytes. NO-donors and iloprost could be useful in the treatment of disorders of blood fluidity.