20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat. Am J Physiol Heart Circ Physiol 2002 Apr;282(4):H1556-65
Date
03/15/2002Pubmed ID
11893593DOI
10.1152/ajpheart.00924.2001Scopus ID
2-s2.0-0036087904 (requires institutional sign-in at Scopus site) 104 CitationsAbstract
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 IC(50) of <15 nM and human recombinant CYP4A11, CYP4F2, and CYP4F3 enzymes with an IC(50) of 42, 125, and 100 nM, respectively. These results indicate that 20-HETE contributes to the acute fall in rCBF after SAH in rats.
Author List
Kehl F, Cambj-Sapunar L, Maier KG, Miyata N, Kametani S, Okamoto H, Hudetz AG, Schulte ML, Zagorac D, Harder DR, Roman RJMESH terms used to index this publication - Major topics in bold
AmidinesAnimals
Carbon Dioxide
Cerebrovascular Circulation
Enzyme Inhibitors
Erythrocytes
Fatty Acids, Unsaturated
Hydroxyeicosatetraenoic Acids
Male
Microscopy, Video
Partial Pressure
Rats
Rats, Sprague-Dawley
Regional Blood Flow
Subarachnoid Hemorrhage
Time Factors
