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

Autori
Kehl, F. ; Cambj-Sapunar, L. ; Maier, K.G. ; Miyata, N. ; Kametani, S. ; Okamoto, H. ; Hudetz, A.G. ; Schulte, M.L. ; Zagorac, D. ; Harder, DR. ; Roman R.J.

Izvornik
American journal of physiology. Heart and circulatory physiology (0363-6135) 282 (2002), 4; H1556-H1565

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Arachidonic-acid; 20-hydroxyeicosatetraenoic acid; Polymorphonuclear leukocytes; Endothelin concentrations; Smooth-muscle; Nitric-oxide; Vasospasm; Arteries; Metabolites; Inhibitor

Sažetak
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 IC50 of <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

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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