Brain eicosanoid levels in spontaneously hypertensive rats after ischemia with reperfusion: leukotriene C4 as a possible cause of cerebral edema.
The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane B2 and 6-keto prostaglandin F1 alpha levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfusion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C4 levels. That the increased brain water content was causally related to an increase in leukotriene C4 was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C4 and brain water contents after reperfusion. Our results indicate that leukotriene C4 is closely associated with an induction of ischemic cerebral edema.
Minamisawa
H
H
Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Terashi
A
A
Katayama
Y
Y
Kanda
Y
Y
Shimizu
J
J
Shiratori
T
T
Inamura
K
K
Kaseki
H
H
Yoshino
Y
Y
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016227:Benzoquinones; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology*; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000235:genetics; D004198:Disease Susceptibility; D004537:Eicosanoic Acids / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D013189:SRS-A / Q000378:metabolism / Q000502:physiology*; D013929:Thromboxane B2 / Q000378:metabolism
D016227:Benzoquinones; D004537:Eicosanoic Acids; D011809:Quinones; D013189:SRS-A; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone