Vascular effects of serotonin and ischemia

Abstract

Circulating 5-hydroxytryptamine originates in the gastrointestinal tract, where it overflows to the blood; part of that serotonin is taken up and stored by the platelets. When the latter aggregate, the released serotonin feeds back on the platelets to amplify the aggregation process; this amplification can be blocked with 5-HT2-serotonergic antagonists such as ketanserin and naftidrofuryl. Serotonin is taken up and destroyed by the endothelial cells; these cells also release endothelium-derived relaxing factor (EDRF) when exposed to the monoamine. The release of EDRF evoked by serotonin is not blocked by 5-HT2-serotonergic antagonists and involves a pertussis toxin-sensitive G-protein. When serotonin reaches vascular smooth muscle it usually causes it to contract; this, in most blood vessels, is prevented by 5-HT2-serotonergic antagonists. The contractions evoked by serotonin are reduced considerably in the presence of a normal endothelium. The same is true for contractions evoked by aggregating platelets, which release enough serotonin to activate receptors on both the endothelial cells (release of EDRF) and on vascular smooth muscle (contraction). Thus, 5-HT2-serotonergic antagonists favor vasodilatation not only because they brake the amplifying effect that serotonin exerts on further platelet aggregation, but also because, by blocking the direct activation of the vascular smooth muscle by platelet-released serotonin, they facilitate the occurrence of endothelium-dependent relaxations to the platelet products. These properties of 5-HT2-serotonergic antagonists help to explain a possible beneficial effect in the treatment of vascular disease, because atherosclerotic blood vessels exhibit a loss of the pertussis toxin-sensitive release of EDRF in response to serotonin, whereas the vasoconstrictor effect of the monoamine is augmented.