Published Online
on April 3, 2003

A more recent version of this article appeared on May 1, 2003

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Submitted on November 6, 2002
Accepted on November 21, 2002

Contribution of 5-Hydroxytryptamine_1B Receptors and 20-Hydroxyeiscosatetraenoic Acid to Fall in Cerebral Blood Flow After Subarachnoid Hemorrhage

Liana Cambj-Sapunar MD; Ming Yu MD, PhD; David R. Harder PhD; and Richard J. Roman PhD^*

From the Department of Physiology (L.C-S., M.Y., R.J.R.) and Cardiovascular Research Center (D.R.H.), Medical College of Wisconsin, Milwaukee.

^* To whom correspondence should be addressed. E-mail: rroman{at}mcw.edu.

Background and Purpose--This study examined the interaction between 5-hydroxytryptamine_1B (5-HT_1B) 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-HT_1B 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-HT_1B 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-HT_1B 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.

Key words: arachidonic acids • cerebral blood flow • head injury • stroke • rats

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