Nitric oxide: a downstream mediator of calcium toxicity in the ischemic cascade.
Loss of cellular calcium homeostasis or the production of nitric oxide (NO) have been cited as possible mechanisms that may contribute to neuronal degeneration during ischemia. We therefore examined whether cellular calcium blockade, using the agent HA1077, was protective during anoxia in hippocampal neuronal cell cultures, and whether the in vitro effects of this drug were linked to the NO pathway. Administration of the agent during anoxia was neuroprotective in neuronal cell culture. In contrast, HA1077 did not protect hippocampal neurons during NO exposure. In addition, inhibition of NO synthesis in conjunction with HA1077 application during anoxia did not significantly increase survival beyond the maximum protection afforded by HA1077 alone. These results suggest that calcium may be an initial messenger in the ischemic cascade, but that subsequent neuronal degeneration is dependent upon the NO pathway.
Maiese
K
K
Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.
Wagner
J
J
Boccone
L
L
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007546:Isoquinolines; D009599:Nitroprusside; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil; D002118:Calcium