NO FUNCTIONAL INVOLVEMENT OF 5-HYDROXYTRYPTAMINE(1A) 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 comp lex 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 ind uced 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 selec tive 5-HT1A receptor agonist flesinoxan (15, 45, and 150 ng/kg/min) in traarterially (i.a.) with N-G-monomethyl-L-arginine (L-NMMA 30 mu g/kg /min) or saline. Forearm blood flow (FBF) was measured by automated R- wave-triggered venous occlusion plethysmography. Forearm vascular resi stance (FVR) was derived from simultaneously recorded i.a. blood press ure (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 functiona lly involved in 5-HT-mediated vasodilatation in human forearm.