Polypeptides, compositions, and methods for treating shock are described. A isolated polypeptide, Deltorphin-E, can be administered without concomitant fluid resuscitation, before, concurrently with, or after the onset of shock or the occurrence of an event that creates a risk of shock. Deltorphin-E can be administered in accordance with the method as part of a preconditioning strategy, which reduces the extent of ischemic injury. Deltorphin-E can be used in preparation for planned ischemia or in a prophylactic manner in anticipation of further ischemic events.