The Role of the Endothelium in the Cardiovascular Response to Serotonin

Serotonin causes constriction of the vascular smooth muscle cells and platelet aggregation mainly through activation of 5-HT2-serotonergic receptors. The vasoconstrictor effects of serotonin can be counteracted by the prejunctional inhibition of adrenergic neurotransmission and predominantly by the release of endothelium derived relaxing factor. These effects of the monoamine are caused by activation of 5-HT1-like serotonergic receptors. Endothelium derived relaxing factor also prevents platelet aggregation and adhesion to the vascular wall. When the endothelium is dysfunctional, as is the case in atherosclerosis or after the endothelium has recovered from an injury, serotonin cannot induce the liberation of endothelium derived relaxing factor but will cause the release of endothelium derived contracting factor. As a result platelet aggregation and vasoconstriction can occur. Serotonin may also increase the viscosity of the blood by an action on red and white blood cells, which may cause a further impairment of blood flow. At the same time platelet derived growth factor, released from aggregating blood platelets may cause proliferation of the vascular smooth muscle cells which participates in the progression of atherosclerosis.