Age, platelet serotonin kinetics and 5HT2-receptor blockade in essential hypertension.
Serotonin (5HT) released from activated platelets causes platelet aggregation and vasoconstriction which are both exaggerated in older age and contribute to the development of thromboembolic complications. Platelet 5HT kinetics and reactivity were investigated in 45 patients with essential hypertension and 45 healthy control subjects matched for age, sex and smoking status. An age-dependent attenuation of total 5HT turnover and platelet 5HT release was revealed in control subjects but not in patients with essential hypertension. In the latter, especially in men, platelet 5HT uptake decreased with age and high blood pressure, leading to elevated 5HT plasma concentration. In parallel, platelet reactivity was increased with advancing age as shown by a greater 5HT induced aggregation and higher beta-thromboglobulin plasma concentration. Antihypertensive treatment with ketanserin resulted in inhibition of 5HT-induced shape change reaction and aggregation as well as a decrease in platelet 5HT release. Age contributes to altered platelet 5HT kinetics and 5HT2-receptor reactivity thereby elevating thromboembolic risk. 5HT2-receptor blockade with ketanserin interferes with these events by inhibition of platelet 5HT release and by a greater antiaggregatory and antihypertensive action in older age.
Amstein
R
R
Department of Research, University Hospital, Basel, Switzerland.
Fetkovska
N
N
Bühler
F R
FR
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D007650:Ketanserin / Q000494:pharmacology; D007700:Kinetics; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000097:blood / Q000187:drug effects; D012701:Serotonin / Q000097:blood*
D011985:Receptors, Serotonin; D012701:Serotonin; D007650:Ketanserin