Change in shear stress (Δτ)/hydraulic conductivity (Lp) relationship after pronase treatment of individual capillaries in situ

A complex glycoprotein meshwork covers the inner wall of blood vessels and is implicated in mechanotransduction of fluid shear stress (τ). A relationship between Δτ and capillary Lp has been established. The purpose of this study was to evaluate Lp in response to Δτ after exposing the capillary lumen to a mild, non-specific protease selected to disrupt its inner matrix. We hypothesized that Lp would not correlate with Δτ after enzyme treatment. Frogs (Rana pipiens, n = 69) were pithed and the mesentery was exteriorized. Lp was assessed at 30 cm H2O using the modified Landis technique after an abrupt, square wave Δτ produced by a physiologically relevant increase in pressure. Perfusate solutions were 10 mg ml− 1 BSA/frog Ringer's (Control) or 0.1 mg ml− 1 pronase in BSA/Ringer's (1 min) then BSA/Ringer's alone (Test). Mean (± SE) control Lp following Δτ was 2.2 ± 0.2 × 10− 7 cm s− 1 cm H2O− 1 and individual values correlated positively with Δτ (r = 0.85, P < 0.0001, n = 41). After pronase, mean Test Lp (17.6 ± 2.5 × 10− 7 cm s− 1 cm H2O− 1) was higher compared to control and Δτ/Lp plots revealed two subsets of capillaries. Lp correlated strongly with Δτ in capillaries with diameters ≤ 15 μm (r = 0.91, P = 0.0006, n = 14) and also in a second subset of capillaries with diameters  > 15 μm (r = 0.96, P = 0.0001, n = 8). Slopes were 3.9- and 8.7-fold higher, respectively, compared to control. These data suggest a protective role for luminal constituents of intact capillaries. Mechanisms involved in capillary responses to flow-induced, mechanical stimuli may be located in the cellular structures that form capillaries.