Extra- and intracellular signaling pathways under red blood cell aggregation and deformability changes

Abstract

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.

Comparison of the Effects of Three Cell Saver Devices on Erythrocyte Function During Cardiopulmonary Bypass Procedure—A Pilot Study

“…It is conceivable that the shear force applied during the CS procedure may directly affect the deformability as well as the shape of RBCs (15,16). The erythrocyte deformability affects the HV (17,18). In our study, although we observed that HV tended to increase after the procedure in these three groups, only Group F yielded statistical significance.…”

Vinpocetine and Pyritinol: A New Model for Blood Rheological Modulation in Cerebrovascular Disorders—A Randomized Controlled Clinical Study

“…Furthermore, drugs that inhibit the phosphodiesterase enzyme (PDE) like pentoxifylline improve blood viscosity via amelioration of erythrocyte deformability; thus vinpocetine reduced the erythrocytes aggregations through cGMP-dependent pathway leading to the improvement in erythrocyte deformability [ 33 ].…”

Neural regulation of cancer: from mechanobiology to inflammation

“…Although the effects of the SNS on cancer cell mechanotype remain to be investigated, activation of β‐adrenoceptor signaling is known to regulate the mechanical properties of other cell types, including blood and muscle cells. Treating red blood cells and airway smooth muscle cells with the β‐adrenoceptor agonist, isoproterenol, makes these cells more deformable 34 , 35 . In contrast, treating primary cardiomyocytes with the same drug makes these cells stiffer 36 .…”