title: Contribution of 5-hydroxytryptamine1B receptors and 20-hydroxyeiscosatetraenoic acid to fall in cerebral blood flow after subarachnoid hemorrhage.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
authors.forename: Liana
authors.initials: L
authors.lastname: Cambj-Sapunar
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: David R
authors.initials: DR
authors.lastname: Harder
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001769:Blood; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology; D020013:Calcium Signaling / Q000187:drug effects; D002555:Cerebrospinal Fluid; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002946:Cisterna Magna; D004537:Eicosanoic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000819:agonists / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000502:physiology*; D007267:Injections; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000150:complications / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000503:physiopathology
chemical_list: D000578:Amidines; D004537:Eicosanoic Acids; D004791:Enzyme Inhibitors; C000708209:HET0016; D006893:Hydroxyeicosatetraenoic Acids; D011412:Propanolamines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C058392:isamoltane; D010741:Phospholipases A