Age and 5HT 2-receptor blockade with ketanserin in essential hypertension.
Platelet derived serotonin (5HT) contributes to blood pressure elevation and the development of thromboembolic complications. Among the pathophysiological mechanisms involved in these vascular events, derangements in 5HT kinetics and exaggerated platelet response to 5HT may be part of the major triggering factors. An age-dependent attenuation platelet 5HT kinetics was revealed in normotensive control subjects but not in patients with essential hypertension. In older hypertensive patients, particularly in men, platelet 5HT uptake was decreased. In parallel, platelet reactivity was increased with advancing age as shown by a greater 5HT induced platelet aggregation and higher plasma concentration of beta-thromboglobulin. Antihypertensive treatment with the 5HT2-receptor antagonist ketanserin attenuated platelet 5HT turnover and inhibited 5HT induced platelet aggregation; the latter was more pronounced in older patients. The clinical efficacy and tolerability of ketanserin 20-40 mg twice daily given as mono- or combination therapy was evaluated in 188 patients with mild to moderate essential hypertension for a period of 12 weeks. A greater fraction of patients greater than or equal to 60 years achieved diastolic target pressure of less than or equal to 95 mgHg. Complaints related to the central nervous system or the peripheral circulation were greatly reduced in patients older than 60 years. In older patients, over and above the antihypertensive effect, 5HT2-receptor blockade may play an important role in the prevention of thromboembolic complications by inhibition of 5HT induced platelet activation.
Bühler
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Amstein
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D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007650:Ketanserin / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists
D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin