The role of 5-hydroxytryptamine and 5-hydroxytryptaminergic mechanisms in hypertension.

1. The possible role of 5-hydroxytryptamine (5-HT) and 5-HT-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 5-HT-receptors. These drugs, like ketanserin, urapidil and flesinoxan are used as tools to study the role of 5-HT and its receptors in hypertension. 2. The following arguments would plead in favour of a certain role of 5-HT and 5-HT-receptors in the pathogenesis and maintenance of hypertension: hyperresponsiveness of blood vessels from hypertensive patients and animals to 5-HT-induced constriction; the antihypertensive/vasodilator activity of the 5-HT2-receptor antagonist ketanserin; enhanced sensitivity of platelets from hypertensives to 5-HT. 3. However, at least as many arguments would deny a role of peripheral 5-HT in hypertension, like for instance: the fact that 5-HT is not a generally accepted pressor agent, whereas its concentration in the circulating blood is subthreshold; the hyperresponsiveness of vessels from hypertensives is not specific for 5-HT; the elevated local concentration of 5-HT released by platelets is mainly limited to the microcirculation; the 5-HT2-receptor antagonist ketanserin is the only agent of this type which lowers blood pressure, other 5-HT2-receptor blockers like ritanserin and LY 53587 being inactive. 4. The various data and arguments available do not unequivocally support a relevant role of peripheral 5-HT and its receptors in hypertensive disease.(ABSTRACT TRUNCATED AT 250 WORDS)