Sumatriptan elicits both constriction and dilation in human and bovine brain intracortical arterioles

Br J Pharmacol. 2001 Jan;132(1):55-62. doi: 10.1038/sj.bjp.0703763.


1. Little is known about serotonin (5-HT) receptors present on brain microvessels that are innervated by brainstem serotonergic neurons. Using 5-HT, sumatriptan and subtype selective 5-HT(1) receptor agonists and/or the 5-HT(1) receptor antagonist GR127935, we characterized the 5-HT receptors involved in regulating microvascular tone of pressurized intracortical arterioles (approximately 40--50 microm) isolated from human and bovine cerebral cortex. The role of nitric oxide (NO) on these responses was assessed with the N(omega)-nitro-L-arginine (L-NNA, 10(-5) M), an inhibitor of NO synthesis. Bovine pial arteries were studied for comparative purposes. 2. At spontaneous tone, 5-HT induced a dose-dependent constriction of human and bovine microarteries (respective pD(2) values of 7.3+/-0.2 and 6.9+/-0.1); a response potently inhibited by GR127935 (pIC(50) value of 8.5+/-0.1) in bovine microvessels. 3. In both species, the 5-HT(1) receptor agonist sumatriptan induced a biphasic response consisting of a small but significant dilation at low concentrations (1 and/or 10 nM) followed by a constriction at higher doses (pD(2) for contraction of 6.9+/-0.1 and 6.6+/-0.2 in human and bovine vessels, respectively). Pre-incubation with L-NNA abolished the sumatriptan-induced dilation and significantly shifted the dose-response of the constriction curve to the left. In contrast, the selective 5-HT(1D) (PNU-109291) and 5-HT(1F) (LY344864) receptor agonists were devoid of any vasomotor effect. 4. In bovine pial vessels, 5-HT and sumatriptan elicited potent constrictions (respective pD(2) of 7.2+/-0.1 and 6.6+/-0.1), a weak dilation being occasionally observed at low sumatriptan concentrations. 5. A significant negative correlation was observed between pial and intracortical vessels diameter and the extent of the dilatory response to 10(-9) M sumatriptan. Together, these results indicate that sumatriptan, most likely via activation of distinctly localized microvascular 5-HT(1B) receptors, can induce a constriction and/or a dilation which is sensitive to inhibition of NO synthesis and dependent on the size and, possibly, the existing tone of the vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterioles / drug effects
  • Benzopyrans / pharmacology
  • Carbazoles / pharmacology
  • Cattle
  • Cerebral Cortex / blood supply*
  • Cerebrovascular Circulation / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Fluorobenzenes / pharmacology
  • Humans
  • Muscle Tonus / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase Type III
  • Nitroarginine / pharmacology
  • Piperazines / pharmacology
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT1
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Sumatriptan / pharmacology*
  • Vasoconstrictor Agents / pharmacology*
  • Vasodilator Agents / pharmacology*


  • Benzopyrans
  • Carbazoles
  • Enzyme Inhibitors
  • Fluorobenzenes
  • LY 344864
  • PNU 109291
  • Piperazines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Nitroarginine
  • Serotonin
  • Sumatriptan
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III