Serotonergic receptors and drugs in hypertension.
The possible role of 5-hydroxytryptamine (5HT) and 5HT-receptors in hypertension, already suggested by Page in 1954, has been subject to a renaissance of interest owing to the development of antihypertensive drugs which interact with 5HT-receptors. These drugs, like ketanserin, urapidil and flesinoxan are used as tools to study the role of 5HT and its receptors in hypertension. Some arguments would plead in favour of a certain role of 5HT and 5HT-receptors in the pathogenesis and maintenance of hypertension: hyperresponsiveness of blood vessels from hypertensive patients and animals to 5HT-induced constriction; the antihypertensive/vasodilator activity of the 5HT2-receptor antagonist ketanserin; enhanced sensitivity of platelets from hypertensives to 5HT. However, there are also several arguments which do not support a causal role of 5HT in hypertensive disease: 5HT is not a generally accepted pressor agent, whereas its concentration in the circulating blood is subthreshold; the 5HT2-receptor antagonist ketanserin is the only agent of this type which lowers blood pressure, other 5HT2-receptor blockers (ritanserin; LY 53587) being inactive. The various data and arguments available do not unequivocally support a relevant role of peripheral 5HT and its receptors in hypertensive disease. 5HT2-receptor blockade may, however, have a favourable effect on the microcirculation under pathological conditions. The stimulation of central 5HT1A-receptors by drugs like urapidil, 8-OH-DPAT or flesinoxan, has been demonstrated to induce peripheral sympathoinhibition and a fall in blood pressure. This mechanism appears to be a novel target for centrally acting antihypertensives, clearly different from that of clonidine and related drugs, which are centrally acting alpha 2-adrenoceptor agonists.
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
P A
PA
van Zwieten
G J
GJ
Blauw
P
P
van Brummelen
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007650:Ketanserin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D014665:Vasodilator Agents; D007650:Ketanserin; C015568:urapidil