Role of endothelins in septic, cardiogenic, and hemorrhagic shock.

Shock is a condition where blood flow is inadequate for tissue needs. In all forms of shock, the concentrations of endothelins (ETs) are elevated, and they are especially high in septic shock. The rise in ETs plasma levels may initially have some positive homeostatic effects, for ETs can help restore normal vascular tone. However, high levels of ETs compromise the appropriate matching of flow to tissue needs and contribute to the pathophysiology of shock. Attempts at regulating the effects of ETs by the use of pharmacological blockers is made complicated by important interactions between the ETA and ETB receptors and potentially different effects on different tissues. We conclude that antagonism of ET receptors is unlikely to be helpful for cardiogenic or hemorrhagic shock. Furthermore, selective blockade is unlikely to be helpful. However, moderate doses of a mixed ET receptor antagonist may be of use for the management of septic patients.