Serotonin, hypertension and vascular disease.
Circulating 5-hydroxytryptamine (5HT, serotonin) 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 platelets aggregate, the released serotonin feeds back on the platelets to amplify the aggregation process; this amplification can be blocked with 5HT2-serotonergic antagonists. 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 prevented by 5HT2-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 5HT2-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, 5HT2-serotonergic antagonists favour vasodilation 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. In addition, these compounds may prevent the stimulatory effect of serotonin on the proliferation of vascular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Vanhoutte
P M
PM
Baylor College of Medicine, Houston, Texas 77030.
D001792:Blood Platelets / Q000502:physiology; D016232:Endothelins / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000517:prevention & control*; D009569:Nitric Oxide / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology*; D012701:Serotonin / Q000097:blood*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000378:metabolism*; D014652:Vascular Diseases / Q000097:blood / Q000517:prevention & control*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D016232:Endothelins; D012702:Serotonin Antagonists; D009569:Nitric Oxide; D012701:Serotonin