However, these clinical findings do not in any way contradict the assumption that endothelin-1 could be involved in the development of migraine auras, because endothelin-1 does not cross the blood–brain barrier and becomes a vasodilator when applied intraluminally instead of abluminally, since it causes the release of nitric oxide (NO) under this condition (Kobari et al., 1994a, b). The gene discussed is EDN1; the disease is migraine with aura.