20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat

2002 ◽  
Vol 282 (4) ◽  
pp. H1556-H1565 ◽  
Author(s):  
Franz Kehl ◽  
Liana Cambj-Sapunar ◽  
Kristopher G. Maier ◽  
Noriyuki Miyata ◽  
Shunishi Kametani ◽  
...  

This study examined the effects of blocking the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) on the acute fall in cerebral blood flow after subarachnoid hemorrhage (SAH) in the rat. In vehicle-treated rats, regional cerebral blood flow (rCBF) measured with laser-Doppler flowmetry fell by 30% 10 min after the injection of 0.3 ml of arterial blood into the cisterna magna, and it remained at this level for 2 h. Pretreatment with inhibitors of the formation of 20-HETE, 17-octadecynoic acid (17-ODYA; 1.5 nmol intrathecally) and N-hydroxy- N′-(4-butyl-2-methylphenyl)formamidine (HET0016; 10 mg/kg iv), reduced the initial fall in rCBF by 40%, and rCBF fully recovered 1 h after induction of SAH. The concentration of 20-HETE in the cerebrospinal fluid rose from 12 ± 2 to 199 ± 17 ng/ml after SAH in vehicle-treated rats. 20-HETE levels averaged only 15 ± 11 and 39 ± 13 ng/ml in rats pretreated with 17-ODYA or HET0016, respectively. HET0016 selectively inhibited the formation of 20-HETE in rat renal microsomes with an IC50of <15 nM and human recombinant CYP4A11, CYP4F2, and CYP4F3 enzymes with an IC50 of 42, 125, and 100 nM, respectively. These results indicate that 20-HETE contributes to the acute fall in rCBF after SAH in rats.

Neurosurgery ◽  
1995 ◽  
Vol 36 (2) ◽  
pp. 358???364 ◽  
Author(s):  
Osamu Fukuda ◽  
Shunro Endo ◽  
Naoya Kuwayama ◽  
Jun Harada ◽  
Akira Takaku

Neurosurgery ◽  
1995 ◽  
Vol 36 (2) ◽  
pp. 358-364 ◽  
Author(s):  
Osamu Fukuda ◽  
Shunro Endo ◽  
Naoya Kuwayama ◽  
Jun Harada ◽  
Akira Takaku

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