Targeting endothelin receptors for pharmacotherapy of ischemic stroke: current scenario and future perspectives

Increased expression of endothelin (ET) peptide and its receptors following ischemic stroke is found to regulate many critical aspects of stroke pathophysiology. Many attempts have been made to target ET receptors in various animal models of stroke, but it is very difficult to draw a definite line of conclusion, because these studies differ in many aspects, such as animal model, treatment schedule, parameters and techniques used for assessing these parameters. A meta-analysis of all studies showed a significant reduction in the lesion volume and improvement in functional outcome in focal cerebral ischemia. ETA receptor antagonists appear to offer an essential advantage of multiple neuroprotective mechanisms, including prevention of blood-brain barrier disruption and leukocyte infiltration.