The relevance of serotonin antagonism in the treatment of hypertension.

The role of serotonin in the pathogenesis of hypertension is not clear. Serotonin is produced by the enterochromaffin cells of the gut; the greater part of this is metabolised in the liver and lungs and nearly all of the remainder is taken up by the platelets. Consequently, circulating levels of serotonin are extremely low. The arterial wall possesses S2-serotonergic receptors, stimulation of which by serotonin leads to vasoconstriction. There are also serotonergic neurons in the central nervous system, particularly in the medulla, which are concerned with the neurogenic control of the circulation. Ketanserin has a high affinity for the S2-receptors, and thus it will antagonise the stimulating effect of serotonin at these receptors. It also has a weaker affinity for alpha 1-adrenoceptors and may act in part by antagonising the pressor effects of norepinephrine, either directly, or indirectly through a link between serotonin S2-receptors and alpha 1-receptors. Experimental evidence suggests that atheromatous lesions lead to increased sensitivity to the vasoconstricting effects of serotonin. This may be due in part to platelet adhesion to areas of endothelial damage, with an associated reduced presence of endothelial relaxing factor. In human hypertension, ketanserin appears to lower blood pressure more effectively in older patients, an effect which may be due to associated atheroma of the aorta and large arteries of these patients. Serotonin antagonism offers a novel approach to the treatment of the hypertensive patient. The increased effectiveness of ketanserin in elderly patients may be of particular importance.(ABSTRACT TRUNCATED AT 250 WORDS)