Serotonergic Receptors and Drugs in Hypertension

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Abstract
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 α2‐adrenoceptor agonists.