Contribution of 5-hydroxytryptamine1B receptors and 20-hydroxyeiscosatetraenoic acid to fall in cerebral blood flow after subarachnoid hemorrhage. Stroke 2003 May;34(5):1269-75
Date
04/05/2003Pubmed ID
12677022DOI
10.1161/01.STR.0000065829.45234.69Scopus ID
2-s2.0-0038304402 (requires institutional sign-in at Scopus site) 81 CitationsAbstract
BACKGROUND AND PURPOSE: This study examined the interaction between 5-hydroxytryptamine1B (5-HT1B) receptors and 20-hydroxyeiscosatetraenoic acid (20-HETE) in contributing to the acute fall in regional cerebral blood flow (rCBF) after subarachnoid hemorrhage (SAH) in rats.
METHODS: The effects of intracisternal injection of 0.3 mL of arterial blood, artificial cerebrospinal fluid, and 5-HT on rCBF and the levels of 20-HETE and 5-HT in cerebrospinal fluid were measured in rats pretreated with vehicle, a 5-HT1B receptor antagonist (isamoltane hemifumarate), or an inhibitor of the synthesis of 20-HETE (HET0016). The effects of HET0016 and isamoltane on the vasoconstrictor response and changes in [Ca2+]i to 5-HT were also studied in middle cerebral arteries and vascular smooth muscle cells isolated from these vessels.
RESULTS: 20-HETE and 5-HT levels in cerebrospinal fluid rose from 172+/-10 to 629+/-44 ng/mL and from 6+/-4 to 1163+/-200 nmol/mL, respectively, after SAH. rCBF fell by 30% 10 minutes after SAH, and it remained at this level for the next 2 hours. Blockade of 5-HT1B receptors prevented the sustained fall in rCBF seen after SAH. Intracisternal injection of 5-HT mimicked SAH by increasing 20-HETE levels in cerebrospinal fluid to 475+/-94 ng/mL and reducing rCBF by 30%. Blockade of the synthesis of 20-HETE with HET0016 prevented the fall in rCBF produced by 5-HT. Isamoltane and HET0016 reduced the vasoconstrictor response of isolated MCA to 5-HT by >60% and diminished the rise in [Ca2+]i produced by 5-HT in vascular smooth muscle cells isolated from these arteries.
CONCLUSIONS: These results suggest that the release of 5-HT after SAH activates 5-HT1B receptors and the synthesis of 20-HETE and that 20-HETE contributes to the acute fall in rCBF by potentiating the vasoconstrictor response of cerebral vessels to 5-HT.
Author List
Cambj-Sapunar L, Yu M, Harder DR, Roman RJMESH terms used to index this publication - Major topics in bold
AmidinesAnimals
Blood
Brain Ischemia
Calcium Signaling
Cerebrospinal Fluid
Cerebrovascular Circulation
Cisterna Magna
Eicosanoic Acids
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Injections
Male
Middle Cerebral Artery
Muscle, Smooth, Vascular
Phospholipases A
Propanolamines
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1B
Receptors, Serotonin
Serotonin
Serotonin Antagonists
Subarachnoid Hemorrhage
Vascular Resistance
Vasoconstriction
Vasospasm, Intracranial
