PMID: 8587428Jan 1, 1995Paper

The endothelin receptor antagonist SB 217242 reduces cerebral focal ischemic brain injury

Journal of Cardiovascular Pharmacology
F C BaroneE H Ohlstein

Abstract

Previously, we demonstrated that cerebral focal ischemic tissue exhibits a significant increase in immunoreactive endothelin (ET). Because increased ET might exacerbate the consequences of cerebral ischemia, we evaluated the effects of the orally active ETA/B receptor antagonist SB 217242 on middle cerebral artery occlusion (MCAO) in the spontaneously hypertensive rat (SHR). SHRs were treated b.i.d. with vehicle or with 3 or 15 mg/kg SB 217242 p.o. for 7 days. Permanent MCAO was performed on day 7 and animals were sacrificed on day 8. Forebrains were stained and the extent of cerebral (i.e., cortical) infarction was determined using image analysis. Hemispheric swelling (%), hemispheric infarct (%), and infarct volume (mm3) were quantitated for each animal. SB 217242 treatment produced a significant decrease in ischemic brain injury. Hemispheric infarction and infarct volume were reduced after the 15 mg/kg treatment (12.0 +/- 1.1% and 69 +/- 6 mm3) compared to vehicle (17.3 +/- 1.5% and 99 +/- 8 mm3) (p < 0.05). No significant effects on hemispheric swelling were observed. This is the first demonstration of an ET receptor antagonist exhibiting efficacy in cerebral focal ischemia. The fact that a 30% reduction in ischemic brain i...Continue Reading

Citations

Oct 6, 2000·Drug Discovery Today·A RayJ B Gupta
Jun 4, 2008·Current Opinion in Cardiology·Brian L StaufferChristopher A DeSouza
May 26, 2005·Brain Research. Brain Research Reviews·Lyle W Ostrow, Frederick Sachs
Mar 11, 2004·The European Journal of Neuroscience·F BlomstrandC Giaume

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