Endothelin Levels Increase in Rat Focal and Global Ischemia

Abstract

Summary: Endothelin-1, a peptide exhibiting extremely potent cerebral vasoactive properties, is elevated in the cerebrospinal fluid after hemorrhagic stroke and impli cated in cerebral vasospasm. The purpose of this study was to determine changes in endothelin in ischemic rat brain by assaying endothelin tissue and extracellular lev els. Immunoreactive endothelin levels in ischemic brain tissue following permanent or transient focal ischemia produced by middle cerebral artery occlusion was deter mined. In addition, endothelin levels were assayed in stri atal extracellular fluid collected by microdialysis before, during, and after global ischemia produced by two-vessel occlusion combined with hypotension. Twenty-four hours after the onset of permanent middle cerebral artery occlusion, the ischemic cortex level (0.58 ± 0.27 fmoll mg protein) of immunoreactive endothelin was signifi cantly (p < 0.05) increased, by 100%, over that in the nonischemic cortex (0.29 ± 0.13 fmollmg protein). TranEndothelin (ET) is a 21-amino acid peptide orig inally isolated from porcine endothelial cells (Yan agisawa et aI., 1988). Three isoforms of endothelin (i.e., ET-l, -2, and -3) have been identified in geno mic DNA (Inoue et aI., 1989). Both ET-l and ET-3 are present in the brain (Matsumoto et aI., 1989; Shinmi et aI., 1989; Takahashi et aI., 1990) and spe cific binding sites have been identified (Koseki et

Bumetanide Inhibition of the Blood-Brain Barrier Na-K-Cl Cotransporter Reduces Edema Formation in the Rat Middle Cerebral Artery Occlusion Model of Stroke

“…There is good evidence, however, that hypoxia and the peptides vasopressin and endothelin, all factors present during ischemia, stimulate activity of the BBB cotransporter. We have found that vasopressin, which is centrally released during ischemia (Dóczi 1993;Landgraf 1992;Ostrowski et al, 1992;Sorensen et al, 1985) and promotes edema formation (Dickinson and Betz, 1992;Dóczi, 1993;Dóczi et al, 1982Dóczi et al, , 1984Hertz et al, 2000;Rosenberg et al, 1990), is also a potent stimulator of the brain microvascular Na-K-Cl cotransporter (O'Donnell et al, 1995a), as is endothelin, which is also released during ischemia (Barone et al, 1994;Kawai et al, 1996bKawai et al, , 1997Spatz et al, 1997). We have shown that vasopressin stimulates the brain endothelial cotransporter by a V1 vasopressin receptor in a manner involving elevation of intracellular [Ca 2+ ] (O'Donnell et al, 1999).…”

Secondhand smoke exposure induces Raf/ERK/MAPK-mediated upregulation of cerebrovascular endothelin ETA receptors

“…It is known that the ET-1 levels in blood and CSF are increased in stroke; this may be further translated to an enhanced receptor-mediated contraction in cerebral arteries [26]. Transcriptional upregulation of ET A and ET B receptors has been reported in rat cerebral arteries after using some injury models like experimental cerebral ischemia and organ culture [10,19,27,28].…”

MEK1/2 inhibition attenuates vascular ETA and ETB receptor alterations after cerebral ischaemia

“…The endothelin system has been shown to be involved in several pathophysiological conditions, such as atherosclerosis (Iwasa et al 1999), heart failure (Miyauchi and Goto 1999) and ischaemic stroke (Ziv et al 1992;Barone et al 1994;Lampl et al 1997). After middle cerebral artery occlusion (MCAO) in cat, there is an enhanced ET mediated constriction in ischaemic vessels (Patel et al 1996b).…”