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 (K) of [C-14-alpha-]aminoisobutyric acid (C-14-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 mul/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 mug 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 mul/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.