Neuroprotective nitric oxide synthase inhibitor reduces intracellular calcium accumulation following transient global ischemia in the gerbil.
By observing the ultrastructural intracellular Ca2+ distribution with Ca(2+)-oxalate-pyroantimonate method, we examined whether the protective mechanism of the nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine (LNNA), involves change of the intracellular Ca2+ movement in delayed neuronal death (DND) in gerbil hippocampal CA1 neurons following 5-min forebrain ischemia. In the group intraventricularly administered 5.0 mg/ml LNNA, 15 min after reperfusion the intracellular Ca2+ deposits and the mitochondrial Ca2+ uptake index increased to levels similar to those in the control group administered only artificial cerebro-spinal fluid, but by 180 min after reperfusion they had returned to the preischemic level. By 15 min after reperfusion Ca2+ deposits in the endoplasmic reticulum (ER) had almost disappeared in both groups, but at 180 min of reperfusion, the ER in only the LNNA group showed Ca2+ deposits. It is suggested that the neuronal toxicity of NO involves the dysfunction of the intracellular Ca2+ transport system including the mitochondria and ER.
Kohno
K
K
Department of Neurological Surgery, Ehime University School of Medicine, Japan. kekob@me1serv.m.ehime-u.ac.jp
Higuchi
T
T
Ohta
S
S
Kohno
K
K
Kumon
Y
Y
Sakaki
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005849:Gerbillinae; D007276:Injections, Intraventricular; D007425:Intracellular Membranes / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D015424:Reperfusion
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D002118:Calcium