Effects of endothelin-1 on blood-brain barrier permeability during focal cerebral ischemia in rats.
The purpose of this study was to determine whether the transport of small hydrophilic molecules across the blood-brain barrier (BBB) during focal cerebral ischemia could be altered by a topical application of endothelin-1 (ET-1) in the ischemic cortex (IC). Forty minutes after middle cerebral artery (MCA) occlusion, patches of 10 nM ET-1 (low-endothelin group), 100 nM ET-1 (high-endothelin group), or normal saline (control group) were placed on the IC of rats for a 20-min period. One hour after MCA occlusion, transfer coefficient (Ki) of [14C-alpha-]aminoisobutyric acid (14C-AIB) or regional cerebral blood flow (rCBF) was determined. Vital signs were not significantly different among the experimental groups. In the control group (n=8), the Ki of the IC was significantly higher than that of the contralateral cortex (CC; 11.9+/-5.8 vs 5.0+/-1.9 microl/g per minute). In the low-endothelin group (n=8), the Ki of the IC was still significantly higher than that of the CC (9.4+/-5.2 vs 5.3+/-2.5 microl/g per minute). However, in the High-endothelin group (n=8), the Ki of the IC was not different from that of the CC (6.9+/-2.1 vs 5.6+/-2.3 microl/g per minute) and 42% lower than that of the control group. The rCBF was not affected by 100 nM of ET-1 [control (n=6): IC 53+/-18 ml/100 g per minute, CC 94+/-23 ml/100 g per minute; high-endothelin (n=6): IC 49+/-15 ml/100 g per minute, CC 98+/-24 ml/100 g per minute]. Our data suggest that the application of endothelin-1 in the IC could reduce the transfer coefficient of small hydrophilic molecules across the BBB during focal ischemia.
Chi
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Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 125 Paterson Street, Suite 3100, New Brunswick, NJ 08901-1977, USA. chi@umdnj.edu
Liu
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Weiss
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D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans
D019332:Endothelin-1