Haitao Wang1, Tao Hong, Huan Wang, Yang Wang. 1. Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, 17 Yong Wai Street, Nanchang 330006, China.
Abstract
BACKGROUND AND PURPOSE: Endothelin-1 (ET-1) plays an important role in the pathogenesis of cerebral vasospasm. Gap junction participates in the pathologic processes of cerebrovascular diseases and may play an important role. The aim of this study is to investigate the role of connexin43 in ET-1-induced contraction in rabbit basilar artery. METHODS: The ET-1-induced contraction without or with carbenoxolone was studied with an isometric tension system. Expression of connexin43 protein in ET-1-stimulated basilar arteries was studied with Western blot. Scrape/scratch method was used to analyse the function of gap junction in cultured rabbit cerebrovascular smooth muscle cells. RESULTS: (1) ET-1 produced a concentration-dependent contraction. Carbenoxolone inhibited ET-1-induced contraction; (2) connexin43 protein level is increased in ET-1-stimulated basilar arteries. Carbenoxolone decreases the connexin43 protein level increased by ET-1; (3) cells treated with ET-1 appeared positive communicate and the dye transfer was increased in a time-dependent fashion; 4 carbenoxolone suppressed the ET-1-induced increases in dye transfer. CONCLUSION: The enhancement of gap junction intercellular communication is activated by ET-1 via modulating the expression of connexin43, and plays an important role in the pathogenesis of cerebral vasospasm. Inhibiting vascular GJIC as a means of reducing cerebral vasospasm after SAH may be of therapeutic advantage.
BACKGROUND AND PURPOSE:Endothelin-1 (ET-1) plays an important role in the pathogenesis of cerebral vasospasm. Gap junction participates in the pathologic processes of cerebrovascular diseases and may play an important role. The aim of this study is to investigate the role of connexin43 in ET-1-induced contraction in rabbit basilar artery. METHODS: The ET-1-induced contraction without or with carbenoxolone was studied with an isometric tension system. Expression of connexin43 protein in ET-1-stimulated basilar arteries was studied with Western blot. Scrape/scratch method was used to analyse the function of gap junction in cultured rabbit cerebrovascular smooth muscle cells. RESULTS: (1) ET-1 produced a concentration-dependent contraction. Carbenoxolone inhibited ET-1-induced contraction; (2) connexin43 protein level is increased in ET-1-stimulated basilar arteries. Carbenoxolone decreases the connexin43 protein level increased by ET-1; (3) cells treated with ET-1 appeared positive communicate and the dye transfer was increased in a time-dependent fashion; 4 carbenoxolone suppressed the ET-1-induced increases in dye transfer. CONCLUSION: The enhancement of gap junction intercellular communication is activated by ET-1 via modulating the expression of connexin43, and plays an important role in the pathogenesis of cerebral vasospasm. Inhibiting vascular GJIC as a means of reducing cerebral vasospasm after SAH may be of therapeutic advantage.
Authors: Luc Leybaert; Paul D Lampe; Stefan Dhein; Brenda R Kwak; Peter Ferdinandy; Eric C Beyer; Dale W Laird; Christian C Naus; Colin R Green; Rainer Schulz Journal: Pharmacol Rev Date: 2017-10 Impact factor: 25.468