Serotonin and the endothelium

Serotonin has many and opposing effects in the cardiovascular system. The vascular endothelium importantly contributes as a modulator and mediator of the cardiovascular effects of serotonin. Endothelial cells contain the enzyme monoaminooxidase which inactivates serotonin. In addition, endothelial cells are a source of vasodilator substances such as endothelium-derived relaxing factor, the endogenous nitrovasodilator. Nitric oxide is continuously formed by the arterial endothelium to inhibit the effects of vasoconstrictor substances such as serotonin. Accordingly, removal of the endothelium enhances contractions induced by serotonin in most vascular preparations. In certain blood vessels, such as the porcine and canine coronary artery, serotonin stimulates the release of endothelium-derived nitric oxide. Endothelium-dependent relaxations to serotonin also occur in intramyocardial porcine coronary resistance arteries. In contrast to porcine and canine arteries, endothelium-dependent relaxations to serotonin have not been demonstrated in the human coronary and internal mammary artery. In the porcine coronary artery with regenerated endothelium and in that with atherosclerotic changes, the endothelium facilitates contractions to serotonin, suggesting that an endothelium-derived contracting factor is released. Since indomethacin prevents this endothelium-dependent facilitation of contractions to serotonin in atherosclerotic porcine coronary arteries, a cyclooxygenase product is likely involved. Similarly, in the aorta of spontaneously hypertensive rats, the endothelium facilitates the contractions to serotonin. Thus, the endothelium can importantly modulate the response to serotonin. While in normal arteries, the cells inhibit the vasoconstrictor effects of the monoamine, the endothelium facilitates its contractions in atherosclerotic and hypertensive blood vessels.