Capillary tone: cyclooxygenase, shear stress, luminal glycocalyx, and hydraulic conductivity (Lp)

Control of capillary hydraulic conductivity (Lp) is the physiological mechanism that underpins systemic hydration. Capillaries form the largest surface of endothelial cells in any species with a cardiovascular system and all capillaries are exposed to the flow-induced force, shear stress (τ). Vasoactive molecules such as prostacyclin (cyclooxygenase product, COX) are released from endothelial cells in response to τ. Little is known about how COX activity impacts capillary Lp. The purpose here was to assess Lp in situ following an acute Δτ stimulus and during COX1/COX2 inhibition. Mesenteric true capillaries (TC) of Rana pipiens (pithed) were cannulated for Lp assessment using the modified Landis technique. Rana were randomized into Control and Test groups. Two capillaries per animal were used (perfusate, 10 mg·mL(-1) BSA/frog Ringer's; superfusate, frog Ringer's or indomethacin (10(-5) mol·L(-1)) mixed in frog Ringer's solution). Three distinct responses of Lp to indomethacin (TC2) were demonstrated (TC1 and TC2 medians: Test Subgroup 1, 3.0 vs. 1.8; Test Subgroup 2, 18.2 vs. 2.2; Test Subgroup 3, 4.2 vs. 10.2 × 10(-7) cm·sec(-1)·cm H2O(-1)). Multiple regression analysis revealed a relationship between capillary Lp and systemic red blood cell concentration or hematocrit, plasma protein concentration, and Δτ (Test Subgroup 1, R(2) = 0.59, P < 0.0001; Test Subgroup 2, R(2) = 0.96, P = 0.002), but only during COX inhibition. Maintaining red blood cell and plasma protein levels within a normal range may control barrier function in a healthy state. Recovering barrier function may be an unrecognized benefit of transfusions during blood loss or edema formation.