Raised endothelin-1 concentration in the plasma and cerebrospinal fluid following cerebrovaficular disease.

Endothelin-1 (ET-) is a potent and long-lasting vasconstricting peptide that causes vasopasm. However, no systematic evaluation of ET has evere been attempted during the acute stage of cerebrovascular disease (CVD). The present study focuses on the evaluation of changes in ET in the plasma and cerebrospinal fluid (CSF) over 2 weeks following an episode of CVD. Patients with CVD were divided into two groups, 8 with occlusive CVD and 9 with hemorrhagic CVD. The ET levels were assessed from measurements of both the plasma and CSF concentrations of ET. We estimated the immunoreactive ET1 by radioimmunoassay in both the plasma and CSF. In occlusive CVD, the plasma level of Et was 4.75± 1.00 pg/ml on day 1, followed by a gradual decrease to 3.86 ± 1.34 pg/ml on day 3, 3.17± 1.34 pg/ml on day 5 and 3.05 ± 1.05 pg/ml on day 7. The level of ET on day 14 had declined to 2.52 ± 1.5 pg/ml. The levels of ET on both day 1 (p <0.025) and day 3 (p <0.025) were significantly higher, when compared with that on day 14. Hemorrhagic CVD also demonstrated higher levels of ET during the acute stage, with 8.7 ± 7.2 pg/ml on day 1 and 5.84 ± 4.65 pg/ml on day 3, followed by decrease on days 5, 7 and 14 to 4.42 ± 1.94, 2.84 ± 1.11 and 2.50 ± 1.26 pg/ml, respectively. The values from day 1 to day 5 were significantly higher than that on day 14 (p <0.025 on both days 1 and 3; p <0.05 on day 5). In addition, 4 patients who underwent repeated measurements of the ET in their CSF showed a decrease from a value of 28.9 ± 5.2 pg/ml on day 1 to 22.0 ± 6/3 pg/ml after 2 weeks. Elevated concentrations of ET-1 in both the plasma and CSF were thus clarified in the present study. In conclusion, the time course of induction of ET production is consistent with the temporal sequence of derangement of the cerebral hemodynamics following CVD, further supporting the hypothesis that ET may also be closely related to the function of the blood-brain and blood-CSF barrier.