Role of endothelin receptors in endothelin-1-induced morphological changes of hepatic sinusoidal endothelial fenestrae: morphometric evaluation with scanning electron microscopy

Endothelin (ET)-1, a potent vasoconstrictor, is involved in the contraction of hepatic sinusoidal endothelial fenestrae (SEF) through ET-1 receptors. To clarify the role of each receptor (R) in ET-1 induced contraction of SEF, we studied the size of hepatic SEF under various experimental conditions. Scanning electron microscopy was used for morphometric analysis of the fenestrae of sinusoidal endothelial cells isolated from male Wistar rats under the following conditions: (1) control, (2) ET-1, (3) Bosentan (ETA-R + ETB-R antagonist) --> ET-1, (4) BQ485 (ETA-R antagonist) --> ET-1. (5) BQ788 (ETB-R antagonist) --> ET-1. Each experiment was based on the observations of 200-205 fenestrae (15-20 fenestrae per cell, two cells per dish and six dishes). The diameter of the endothelial pores of the isolated sinusoidal endothelial cells was 123 +/- 35 nm in group (1), 46 +/- 21 nm in group (2), 130 +/- 40 nm in group (3), 72 +/- 28 nm in group (4), and 130 +/- 27 nm in group (5). The differences between groups (2) and (4), and between groups (2) and (5), were statistically significant (P < 0.05, P < 0.01, respectively). Endothelin B receptor (ETB-R) antagonist pretreatment abolished the ET-1-induced contraction of SEF, whereas endothelin A receptor (ETA-R) antagonist pretreatment appeared to partially block this contraction. The present findings indicate that ETB-R plays a primary role in endothelin-1 induced SEF morphological changes, while ETA-R plays a subsidiary role. (C) 2002 Elsevier Science B.V. All rights reserved.