Endothelin-1 exacerbates focal cerebral ischemia without exerting neurotoxic action in vitro.

In a model of focal cerebral ischemia in mice, intracisternal injection of 5 and 10 pmol/mouse endothelin-1 significantly increased the infarcted surface area by 15.5% and by 23.5%, respectively. Endothelin-1 (0.01, 1, and 100 nmol/l) added to the primary neuronal cultures of chick embryo cerebral hemispheres for 1 h and 24 h did not influence the viability of the neurons or the protein content of the cultures. When applied simultaneously with 1 mmol/l sodium cyanide for 30 min, endothelin-1 (0.01, 1, and 100 nM) did not modify the hypoxia-induced changes. The results show that exogenously applied endothelin-1 could exacerbate cerebral ischemia, probably due to its vasoconstrictive properties and not to a direct neurotoxic effect.