Platelet serotonin-LDL interaction in essential hypertension.
Serotonin (5-HT) released from activated blood platelets plays a pivotal role in the development of thromboembolic complications. Essential hypertension, elevated plasma cholesterol, older age, and smoking are predisposing factors for these vascular events, and they all lead to platelet activation. In hypertensive patients, platelet 5-HT uptake is reduced with increasing age and blood pressure. This uptake inhibition is paralleled by an exaggerated platelet shape change and aggregation response. As a consequence, periplatelet 5-HT plasma concentrations are increased and promote further platelet aggregation and vasoconstriction. Low-density lipoproteins (LDL) induce a platelet shape change reaction and amplify the aggregatory response to serotonin. This effect is enhanced in smokers and even greater in hypertensive patients. LDL also inhibit endothelium-dependent relaxations to serotonin thereby unmasking the vasoconstrictor effect. 5-HT2-Receptor blockade with ketanserin interferes with this chain of events at several sites. Ketanserin inhibits platelet 5-HT release and 5-HT-induced platelet aggregation. It exerts a beneficial influence on the lipid profile. Blockade of 5-HT2 receptors leads to direct vascular smooth muscle dilatation as well as unopposed activation of endothelial 5-HT1-like receptors with the subsequent release of endothelium-derived relaxing factor. Taken together, the antihypertensive agent ketanserin may provide a new approach for multiple risk factor intervention therapy, eventually to prevent thromboembolic complications.
Amstein
R
R
Department of Research, University Hospital, Basel, Switzerland.
Fetkovska
N
N
Bühler
F R
FR
D000328:Adult; D000367:Age Factors; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007650:Ketanserin / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D012701:Serotonin / Q000378:metabolism / Q000493:pharmacokinetics / Q000502:physiology*; D012737:Sex Factors; D012907:Smoking / Q000097:blood
D008077:Lipoproteins, LDL; D012701:Serotonin; D007650:Ketanserin