A.V. Muravyov, S.V. Bulaeva, P.V. Mikhailov, I.A.Tikhomirova, A.A. Muravyov

The accumulation of scientific information about blood flow, blood cellular deformability and a reversible erythrocyte association called aggregation led to formation of to new branches of science: first one was Biorheology - the system of knowledge about deformation and flow the biological structures in the whole and second one was Hemorheology - the system of knowledge about deformation and flow of whole blood and its cellular elements. At present they consider the blood as a complex liquid, with its fluidity depending on four main factors: 1) plasma viscosity, 2) hematocrit, 3) aggregation and 4) deformability of red blood cells. Besides blood flow efficiency depends strongly on the shear stress and rate as well vascular geometry. The latter is a very important in microcirculation in particular. At this level of the circulation the red cell microrheology plays a significant role. In the microcirculation, where cells must deform to pass through narrow capillaries, cellular rheology (i.e. the deformability of individual cells) is a major determinant of resistance to flow. An unusual combination of membrane properties allows the RBC to undergo extensive deformation without cell fragmentation, enabling it to effectively perform its function of oxygen delivery during its long life span in circulation. Another microrheological property of red blood cells (RBCs) is their ability to form aggregate under the low flow conditions, mainly in form of rouleaux. Previous rotational viscometric studies showed that the apparent viscosity of blood increased at low shear rates and that this rise is primarily due to red blood cell aggregation. As this effect occurs in the physiological range of shear rates in venous vessels, it was believed that red blood cell aggregation is an important determinant of venous resistance. In this connection it was supposed that the marked changes of red blood cell microrheological properties such as red cell deformability and aggregation mediated an activation of the molecular control mechanisms. RBCs have traditionally been viewed as simple conduits for oxygen transport; however, these cells contain a broad range of signaling molecules. Some of the most well-studied signaling pathways in RBCs are mediated by the second messengers cyclic adenosine monophosphate (cAMP), generated by the conversion of adenosine triphosphate (ATP) to cAMP via membrane-associated adenylyl cyclase and Ca2+  Calmodulin. The analysis of the microrheological change mechanisms showed that the RBC microrheology alteration is connected with an activation of extra-and intra cellular signaling pathways. 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 RBCD increase was mainly associated with an activation of the adenylyl-cyclase-cAMP system. In addition the obtained data made us believe that signaling molecules can directly stimulate the cellular tyrosine kinase activity and can facilitate red cell deformability and aggregation changes. Thus the control of the main red cell microrheological properties are connected with oxygen transport efficiency might be realized under an activation of the molecular signaling pathways.