The role of endothelin-1 and nitric oxide in cerebral ischemia

The effect of cerebral ischemia/reperfusion on vascular responses and endothelin (ET) content in cerebrospinal fluid was investigated in the presence and absence of N omega-nitro-L-arginine (NLA), the nitric oxide (NO) inhibitor. A single intraperitoneal injection of NLA (4 h prior to the induction of ischemia) stereospecifically increased systemic blood pressure (SBP) and reduced the transient, initial (early) recovery of cerebral blood flow (CBF). However, NLA treatment did not significantly affect the late hypoperfusion observed in either Ringer's- or N omega-nitro-D-arginine methyl ester (D-NAME)-treated animals. Both the early and late hypoperfusion coincided with the increased content of ET-1 in the cerebrospinal fluid. These findings strongly suggest that endogenously released ET-1 is responsible for the observed postischemic hypoperfusion.