People with MS exhibit reduced cerebral blood flow. In previous research we found that this appears to be caused by increased secretion of a potent vasoconstrictive substance called endothelin-1 from the astrocytes located in the focal MS plaques. We also demonstrated that by administering an endothelin-1 antagonist the cerebral blood flow was able to recover in the short term. There are indications that chronically reduced cerebral blood circulation can lead to the deterioration of cognitive functions, fatigue and slow progressive death of neurons, which are all elements that can occur with MS and for which no treatment yet exists. In this project we want to examine whether more prolonged treatment with an endothelin-1 antagonist can improve these processes in patients with MS.