We study extreme hemodilution to a hematocrit (Hct) of 11% induced by three plasma expanders: polyethylene glycol conjugated albumin (PEG-Alb), 6% Dextran 70 kDa, and 6% Dextran 500 kDa. The experimental component of our study relies on the microelectrodes and cardiac output to measure both the rheological properties of plasma-expander blood mixtures and the nitric oxide (NO) bioavailability in vessel walls. The modeling component consists of an analysis of the distribution of wall shear stress (WSS) in the microvessels. Our experiments demonstrate that plasma expansion with PEG-Alb causes a state of supra-perfusion with cardiac output 40% above baseline, significantly increases NO vessel-wall bioavailability, and lowers peripheral vascular resistance. We attribute this behavior to the shear thinning nature of blood and PEG-Alb mixtures. To substantiate this hypothesis, we develop a mathematical model of non-Newtonian blood flow in a vessel. Our model employs the Quemada rheological constitutive relationship to express blood viscosity in terms of both Hct and shear rate. The model reveals that the net effect of the hemodilution induced by relatively low-viscosity shear-thinning PEG-Alb plasma expanders is to reduce overall blood viscosity and to increase the WSS, thus intensifying endothelial NO production. These changes act synergistically, significantly increasing cardiac output and perfusion due to lowered overall peripheral vascular resistance.