Effect of thromboxane synthetase inhibitor on cerebral circulation and metabolism during experimental cerebral ischemia in spontaneously hypertensive rats.
The protective effect of thromboxane synthetase inhibitor, OKY-046, on brain ischemia was studied in spontaneously hypertensive rats. Cerebral ischemia was developed by bilateral carotid artery ligation (BCL) for 1 or 3 h and thereafter, circulation was restored for 15 min. OKY-046, 5 or 30 mg/kg, or saline as control was administered i.v. before BCL. Neither blood pressure nor blood gases were altered by OKY-046 or saline injection. During BCL, cerebral cortical blood flow was reduced to 25 and 15% of the resting value at 30 and 60 min, respectively, and these changes were not different among the groups. In rats with ischemia longer than 1 h, the blood flow was well preserved by OKY-046, 30 mg/kg, to 10-17% of the resting level, thus significantly higher than that (less than 5%) in non-treated rats. After 15 min recirculation, the supratentorial lactate level was lower and adenosine triphosphate (ATP) was higher in OKY-046-treated rats than in the saline-treated ischemic rats. Plasma thromboxane B2 was increased markedly in 1 h ischemic-reperfused rats without treatment and the increase was almost completely inhibited by OKY-046. In contrast, 6-keto-prostaglandin F1 alpha was increased 8.5-fold after ischemia and the increase was not affected by the treatment. OKY-046 seems to have an antiischemic effect on acutely induced cerebral ischemia. Selective inhibition of thromboxane A2 production and an inversely high level of prostaglandin I2 may be an important contribution to protection of the microcirculation during ischemia and preservation of ischemic cerebral metabolism.
Sadoshima
S
S
Second Department of Internal Medicine, Kyushu University, Fukuoka City, Japan.
Ooboshi
H
H
Okada
Y
Y
Yao
H
H
Ishitsuka
T
T
Fujishima
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002545:Brain Ischemia / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D007773:Lactates / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007773:Lactates; D008689:Methacrylates; D011773:Pyruvates; D013928:Thromboxane A2; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel