EDN1 and central nervous system disorder: This effect was found to be due to the stimulation of ETB receptor with subsequent activation of nitric oxide synthase and protein kinase C. The release of ET-1 has been apparent in a number of CNS disorders including HIVE (Hartz et al. 2004) and AIDS dementia complex however the effect of ET-1 on brain capillary permeability remains controversial, with some studies claiming that ET-1 significantly increases brain permeability and others suggesting no effect.