Secretory response of endothelin‐1 in cultured human glomerular microvascular endothelial cells to shear stress

Abstract

The shear‐induced secretory response of endothelin‐1 (ET‐1) by human microvascular endothelial cells was studied using paired human glomerular microvascular endothelial cell (HGMEC) cultured monolayers exposed to steady‐state laminar shear stress for up to 10 hours. The first cell monolayer was subjected to a shear stress of 0.65 N m⁻² and the second, 1.3 N m⁻². ET‐1 secretion was determined by radioimmunoassay. Over 10 hours of shear, the total cumulative secretion of ET‐1 was 237.4 pg/cm² for the monolayer exposed to 1.3 N m⁻² and 143.6 pg/cm² for the monolayer exposed to 0.65 N m⁻². The average ET‐1 secretion rate was 20.90±2.15 and 12.45±1.05 pg/cm².h at 0.65 N m⁻² and 1.3 N m⁻², respectively. The results showed that ET‐1 secretion varied with the time of shear in a nonlinear fashion. Although the level of shear stress affected the absolute value of ET‐1 cumulative secretion and secretion rate, the major secretion period for both monolayers occurred between 2.0 and 8.0 hours, with the peak secretion rate occurring at approximately 5 hours. Thus, the response of cultured human microvascular endothelial cells to shear stress differed from that of large vessel endothelial cell cultures in terms of ET‐1 secretion. In addition to the level of shear stress, the time of shear was also an important determinant of ET‐1 secretion. Consequently, the heterogeneity of vascular endothelial cells and the time of shear should both be considered in future research on the secretion of vascular endothelial cell cultures.