 When applied directly to the brain of rats in picomolar quantities as an experimental model of stroke, endothelin-1 caused severe metabolic stimulation and seizures with substantial decreases in blood flow to the same brain regions, both effects mediated by calcium channels.A similar strong vasoconstrictor action of endothelin-1 was demonstrated in a peripheral neuropathy model in rats.Mutations in the EDNRB gene are associated with ABCD syndrome and some forms of Waardenburg syndrome.