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This study was designed to investigate the dependency of the red blood cell deformability upon activation of extra-and intracellular signaling pathways. Exposures of red blood cells (RBCs) to catecholamines and to insulin led to positive change in the RBC deformability. When forskolin, a stimulator of adenylyl cyclase (AC), was added to RBC suspension, the RBC deformability was increased. Somewhat more significant deformability rise appeared after RBC incubation with dB-AMP. The inhibitors of phosphodiesterase (PDE) activity increased red cell deformability. These results revealed a considerable role of the AC-cAMP signaling system in the regulation of red blood cell deformability. The rise of the red blood cell Ca 2+ influx, stimulated by mechanical loading or A23187 was accompanied by a marked lowering of RBC deformability. At the same time blocking of Ca 2+ entry into RBC by verapamil or Ca 2+ chelating by EGTA led to significant deformability rise. The comparison of the effect of the different protein kinases on the red blood cell deformability showed that it was altered more considerable under PKA activation by forskolin or dB-cAMP than by other protein kinases. There was a lesser but quite statistically significant effect of tyrosine protein kinase (TPK) on RBC microrheology. Whereas the microrheological effect of PKC was not so considerable. The problem of the short-term regulation of red blood cell microrheology is examined. The latter includes: the modes of activation of extra-and intracellular molecular signaling pathways, ligand -receptor interaction, second messengers, membrane protein phosphorylation.On the whole the total data clearly show that the red cell deformability changes are connected with activation of different extra -and intracellular signaling pathways. It seems reasonable to suppose that red blood cell deformability changes were mainly associated with activation of the AC-cAMP-PKA pathway, and with decrease of Ca 2+ entry into cells.

Complex impairment of peripheral blood flow in CHF including restricted microcirculation, attenuated regulatory mechanisms and impaired hemorheological properties caused the reduced oxygen utilization contributing to symptoms and advance of heart failure.

Exposure of red blood cells (RBCs) to catecholamines (epinephrine, phenylephrine, an agonist of α 1 -adrenergic receptors, clonidine, an agonist of α 2 -adrenergic receptors and isoproterenol, an agonist of β-adrenergic receptors) led to change in the RBC microrheological properties. When forskolin (10 µM), an AC stimulator was added to RBC suspension, the RBC deformability (RBCD) was increased by 17% (p < 0.05). Somewhat more significant deformability rise appeared after RBC incubation with dB-AMP (by 27%; p < 0.01). Red blood cell aggregation (RBCA) was significantly decreased under these conditions (p < 0.01). All drugs having PDE activity increased red cell deformability similarly. Some more changes of deformability was found after RBC incubation with pentoxifylline -25% (p < 0.05) and IBMX incubation was accompanied only by 15% rise of RBC deformability. The drugs with PDE inhibitory activity reduced red cell aggregation. The most significant RBCA reduction effect was found under cell incubation with pentoxifylline and inhibitor PDE 1 -vinpocetine. On the whole RBCA reduction averaged 36% (p < 0.05) under RBCs incubation with PDE inhibitors. The rise of Ca 2+ influx, stimulated by A23187, was accompanied by an increase of RBCA, whereas red cell deformability was changed insignificantly. At the same time Ca 2+ entry blocking into the red cells by verapamil or its chelating in medium by EGTA led to significant RBCA decrease and deformability rise (p < 0.05).On the whole the total data clearly show that the red cell aggregation and deformation changes were connected with an activation of the different intracellular signaling pathways. It seems reasonable to suppose that RBCA decrease was mainly associated with an activation of the adenylyl-cyclase-cAMP system, while the red cell deformability was closely associated with Ca 2+ control mechanisms.

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