Mechanotransduction and the homeostatic significance of maintaining blood viscosity in hypotension, hypertension and haemorrhage

The increase of plasma and blood viscosity is usually associated with pathological conditions; however, elevation of both parameters often results in increased perfusion and the lowering of peripheral vascular resistance. In extreme haemodilution, blood viscosity is too low and insufficient to maintain functional capillary density, a problem that in experimental studies is shown to be corrected by increasing plasma viscosity up to 2.2 cP. This effect is mediated by mechanotransduction-induced nitric oxide (NO) production via shear stress in the endothelium as shown by microelectrode perivascular measurements of NO concentration. Moderate elevations of blood viscosity by increasing haematocrit (similar to 10%) result in comparable reductions of blood pressure and peripheral vascular resistance, an effect also NO-mediated as it is absent after N omega-nitro-L-arginine methyl ester treatment and in endothelial nitric oxide synthase-deficient mice. These findings show that the rheological properties of plasma affect vessel diameter in the microcirculation leading to counterintuitive responses to the changes in blood and plasma viscosity. Application of these findings to haemorrhagic shock resuscitation leads to the concept of hyperosmotic-hyperviscous resuscitation as a modality for maintaining the recovery of microvascular function.