No functional involvement of 5-hydroxytryptamine1A receptors in nitric oxide-dependent dilatation caused by serotonin in the human forearm vascular bed.
The vascular effects of serotonin (5-hydroxytryptamine, 5-HT) are complex and heterogeneous. In human forearm, we showed that low doses of 5-HT cause marked but transient vasodilatation followed by a persistent vasodilator response. In in vitro and in animal experiments, 5-HT induced release of nitric oxide (NO) through stimulation of endothelial 5-HT1-like receptors. In the present study, we investigated involvement of the "NO pathway" and possible involvement of the 5-HT1A receptor subtype in 5-HT-induced persistent vasodilator response. In 8 healthy volunteers, we infused 5-HT (0.1, 0.3, and 1 ng/kg/min) and the selective 5-HT1A receptor agonist flesinoxan (15, 45, and 150 ng/kg/min) intraarterially (i.a.) with NG-monomethyl-L-arginine (L-NMMA 30 micrograms/kg/min) or saline. Forearm blood flow (FBF) was measured by automated R-wave-triggered venous occlusion plethysmography. Forearm vascular resistance (FVR) was derived from simultaneously recorded i.a. blood pressure (BP) and FBF. 5-HT dose-dependently decreased FVR (p < 0.001). The persistent vasodilator response to 5-HT appears to be mediated by NO release, as suggested by its complete abolition by L-NMMA (p < 0.001). Flesinoxan decreased FVR slightly, but only at high doses (p < 0.05). The present findings indicate that 5-HT1A receptors are not functionally involved in 5-HT-mediated vasodilatation in human forearm.
Bruning
T A
TA
Department of Nephrology, University Hospital Leiden, The Netherlands.
van Zwieten
P A
PA
Blauw
G J
GJ
Chang
P C
PC
D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005542:Forearm; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D010991:Plethysmography; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000097:blood / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012701:Serotonin; C056895:flesinoxan; D001120:Arginine