Red blood cell microrheological changes and drug transport efficiency

Abstract

The purpose of this study was to estimate drug effect on red blood cell (RBC) microrheological properties making for blood transport efficiency. It is well known that blood flow in microcirculation, tissue perfusion and oxygenation depend on red blood cell (RBC) microrheological properties, namely deformability (RBCD) and aggregability (RBCA). In turn the changed red cell mechanical properties can influence the tissue oxygenation as well as the drug delivery to tissues. The exposure of RBCs to agonist of -adrenergic receptors (isoproterenol) caused RBCA decrease and an increase of their deformability. The prostaglandin E1, prostacyclin and insulin showed the similar positive microrheological effect. Neutral microrheological effect was fixed after cell incubation with 5-fluorouracil, rolipram and phorbol 12-myristate 13-acetate; no significant alterations of microrheological properties were found. The agonists of -adrenergic receptors and prostaglandin F2 showed the negative microrheological effect: RBCD was markedly worsened and RBCA was enhanced by 49-60%. It was found that three PDE inhibitors: vinpocetine, rolipram and cilostasol - significantly decreased RBCA and increased RBCD. Therefore PDEs might be considered as red blood cell molecular targets for some drugs. Stimulated by A23187 Ca 2+ influx was accompanied by an increase of RBCA and a decrease of RBCD. The blocking of Ca 2+ entry into the RBCs by verapamil led to a significant positive RBC changes. Therefore the red cell membrane Ca 2+ channels can be considered as molecular targets responsible for red cell microrheology modifications too. Taken together the obtained data showed that the drugs infused in blood flow can interact with blood cells, including the most numerous cell population - red blood cells. This interaction can lead to an alteration of RBC microrheological properties and blood transport possibilities at least according to three abovementioned scenarios.