期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 20, 期 3, 页码 499-504出版社
SAGE PUBLICATIONS INC
DOI: 10.1097/00004647-200003000-00008
关键词
endothelin; endothelin receptor type A antagonist; focal ischemia; middle cerebral artery occlusion; neuroprotection
资金
- NINDS NIH HHS [NS20020] Funding Source: Medline
The authors examined the effect of selective endothelin (ET) receptor type A (ETA) antagonism on histological and functional recovery in cat at 24 hours after reversible middle cerebral artery occlusion (MCAO). A novel and specific ETA antagonist, Ro 61-1790 [5-methylpyridine-2-sulfonic acid-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-1H-tetrazol-5-yl-pyridin-4-yl)-pyrimidin-4-ylamide sodium salt (1:2)1 (Roche, Basel, Switzerland), was used at doses that produced steady-state plasma concentrations and abolished ET-induced pial arteriolar vasoconstriction. In a cranial window preparation. 8 nmol/L ET constricted pial arterioles by 33 +/- 18% (mean +/- SD), but this response was ablated by intravenous Ro 61-1790 treatment (10-mg/kg bolus, 4-mg/kg/h infusion). In additional animal cohorts, halothane-anesthetized cats were treated with 90 minutes of MCAO and 24 hours of reperfusion. Animals received Ro 61-1790 infusion beginning at the onset of reperfusion and continuing for 6 or 24 hours (n = 41). Control cats were treated with 0.9% saline by intravenous infusion throughout reperfusion. There was no difference in injury volume or neurologic evaluation score in saline-treated cats (n = 11; caudate 24 +/- 28%, cortical injury 7.5 +/- 5% of ipsilateral structure; score 52 +/- 8) versus the results in cats treated with Ro 61-1790 for either 24 hours (n = 6; caudate 22 +/- 23%, cortex 6 +/- 5%, injury volume of ipsilateral structure; score 55 +/- 3) or 6 hours (n = 11; caudate 33 +/- 30%, cortex 12 +/- 14%, injury volume of ipsilateral structure; score 50 +/- 19). Mortality was greatest in the 24-hour drug treatment group. These data suggest that blockade of ETA receptor activity is not beneficial to tissue or functional outcomes from experimental stroke in cat.
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