The effect of indomethacin on healthy frog capillaries following a shear stress stimulus : potential clinical implications

Abstract

When cultured endothelial cells are stimulated by shear stress they release prostaglandins. One of the effects of prostaglandin release is vasodilation. The effect of prostaglandins on hydraulic conductivity (Lp) is not known. Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) that is known to block prostaglandins. The purpose of this study was to evaluate the effect of indomethacin on endothelial cells of a true capillary. It was hypothesized that in an intact healthy capillary, superfused with indomethacin, there will be a decrease in capillary Lp after a shear stress stimulus. The mesentery of healthy North American leopard frogs (n=16) was exposed and a capillary was cannulated. Using the modified Landis technique Lp was assessed, after a shear stress stimulus, in a control capillary and a capillary that was exposed to indomethacin. There was not a significant decrease (P=0.13) in Lp when comparing the control vessels with treatment vessels. Data from this study suggest that prostaglandins are not involved with the response of Lp to shear stress in healthy frogs. Since Lp did not decrease in the presence of indomethacin, it is probable that other processes are affecting the response of the endothelium. The clinical implications of this study are important because of the potentially devastating impact of the toxic effects of NSAIDs.