Increased plasma endothelin-1 concentration in patients with acute cerebral infarction and actions of endothelin-1 on pial arterioles of rat.

ABSTRACT

In acute cerebral ischemia there are severe damages of endothelium which have been recognized as the stimuli to secrete endothelin-1, an endothelium-derived peptide and the most potent vasoconstrictor ever known. This study was to measure plasma endothelin-1 level in patients with cerebral infarction and explore the relationship between endothelin-1 and ischemic stroke. The possible involvement of endothelin-1 in local regulation of cerebral arterioles was also investigated. Plasma levels of endothelin-1 were measured by radioimmunoassay in 21 patients. Using a micro-video system, the endothelin-1 actions were also observed on rat pial arterioles in vivo, and with incomplete cerebral ischemia model (rat), effect of ischemia affects the endothelin-1 action. There was a marked increase in plasma endothelin-1 level in the patients and the elevation persisted during the acute and subacute period of stroke. There was a positive correlation between the peptide concentration 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 arteriole contraction after subdural administration. Arteriole calibers were 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. Cerebral ischemia significantly enhanced the action of endothelin-1 (96.4% +/- 7.2% vs 58.2% +/- 6.8%). Endothelin-1 plays an important role in regulating local circulation of ischemic brain. The notable and lasting increase in plasma level of endothelin-1 are associated with cerebral ischemia and infarction.(ABSTRACT TRUNCATED AT 250 WORDS)