INCREASED PLASMA ENDOTHELIN-1 CONCENTRATION IN PATIENTS WITH ACUTE CEREBRAL INFARCTION AND ACTIONS OF ENDOTHELIN-1 ON PIAL ARTERIOLES OF RAT

In acute cerebral ischemia there are severe damages of endothelium whi ch have been recognized as the stimuli to secrete endothelin-1, an end othelium--derived peptide and the most potent vasoconstrictor ever kno wn. This study was to measure plasma endothelin-1 level in patients wi th cerebral infarction and explore the relationship between endothelin -1 and ischemic stroke. The possible involvement of endothelin-1 in lo cal regulation of cerebral arterioles was also investigated. Plasma le vels of endothelin-1 were measured by radioimmunoassay in 21 patients. Using a micro video system, the endothelin-1 actions were also observ ed on rat pial arterioles in vivo, and with incomplete cerebral ischem ia model (rat), effect of ischemia affects the endothelin-1 action. Th ere was a marked increase in plasma endothelin-1 level in the patients and the elevation persisted during the acute and subacute period of s troke. There was a positive correlation between the peptide concentrat ion and infarct size (r = 0.655, P<0.01). In rats, endothelin-1 (dose range: 10(-10) mole / L -10(-7) mole / L) induced a dose-dependent art eriole contraction after subdural administration. Arteriole calibers w ere decreased by 27.7% +/- 3.8% (10(-9) mole / L), 46.8% +/- 4.9% (10( -8) mole / L) and 78.5% +/- 4.7% (10(-7) mole / L), respectively. Cere bral ischemia significantly enhanced the action of endothelin-1 (96.4% 7.2% vs 58.2% +/- 6.8%). Endothelin-1 plays an important role in regu lating local circulation of ischemic brain. The notable and lasting in crease in plasma level of endothelin-1 are associated with cerebral is chemia and infarction. The peptide seems to be involved in the pathoph ysiology of acute cerebral ischemia and plays a deleterious role in th e progress of cerebral infarction.