The endothelial glycocalyx (EG) should play a key role in mediating shear stress to the endothelial surface and triggering the production of NO. The functional impact of colloids on vasodilatation induced by shear stress in isolated perfused hearts (guinea pig) was compared by augmenting Krebs-Henseleit buffer with 1/3 volume 5% human albumin, 6% hydroxyethyl starch (HES) 200/0.5 or 6% HES 450/0.7. Perfusion was also performed after enzymatic digestion of the EG (heparinase, 10IU over 15min) and with application of NO-L-Arginine (10^-5M). Albumin, in contrast to HES, caused a dramatic increase in coronary flow: 9.50 ± 1.09, 5.10 ± 0.49 and 4.87 ± 1.19 ml/min/g for groups "5% Albumin", "HES 200" and "HES 450", respectively (n = 7 each). Dilatation by albumin was diminished both by NO-L-Ag and heparinase to about the same extent; the effects were not additive. Blocking NO production, but not stripping away the heparan sulfates from the EG significantly suppressed coronary flow during infusion of HES 450. Flows during NO-L-Ag infusion reflect the dynamic viscosity of the applied perfusates. Due to its special interaction with the EG, infusing albumin induces greater NO release than HES and so significantly increases coronary flow. However, the large HES 450 molecule may be able to cause some production of NO by shear stress via an interaction even with a rudimentary EG.