Serotonin, norepinephrine, and histamine mediation of endothelial cell barrier function in vitro

Publisher Website
Google Scholar
Abstract
The effects of serotonin (5‐hydroxytryptamine, 5‐HT), norepinephrine (NE), and histamine on endothelial cell barrier function were examined in vitro. Bovine aortic endothelial (BAE) cells grown to confluence on microcarriers formed a measurable barrier to the passage of a trypan blue dye‐bovine serum albumin conjugate (TB‐BSA) from the culture medium into the microcarrier matrix. Vascular smooth muscle (VSM) cells or Swiss 3T3 fibroblasts impeded TB‐BSA diffusion only 42% and 56%, respectively, relative to BAE cells. These results suggest that barrier formation may be an endothelial cell‐specific phenomenon. Treatment of BAE cells with histamine was associated with 2‐to 3‐fold increases in the rate of TB‐BSA diffusion. In contrast, treatment with 5‐HT or NE at concentrations ranging from normal to pathophysiological circulating plasma levels significantly impeded TB‐BSA diffusion by up to 43% and 33%, respectively, relative to untreated controls. The barrier‐modulating effects of the vasoactive amines were dose‐dependent, cell‐specific, and in some cases appear to be receptor‐mediated. These results are consistent with previous reports that histamine increases vascular permeability in part by affecting diffusion between endothelial cells; they support the hypothesis that 5‐HT and NE contribute to the maintenance of the endothelial barrier in vivo.