Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin.

Abstract

SUMMARY Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of Sj-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S 2 -serotoniiiergic antagonist with additional ai-adrenergic blockmg properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes In cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either /3-adrenergic biockers or diuretics. Several studies have shown a greater efficacy in older (> 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S 2 -serotoninergic or a,-adrenergic blockade alone, but an interaction between the two effects appears to be required.

Association study of the 5-HT2A receptor gene polymorphism, T102C and essential hypertension

“…7,8 5-HT 2A and 5-HT 2B receptor subtypes belong to the 5-HT 2 family of serotonin receptors and have been implicated in hypertension and other forms of cardiovascular disease such as pulmonary hypertension and atheroschlerosis due to their vasoconstrictive role 9 The 5-HT 2A receptor antagonist ketanserin has an antihypertensive action as the results of most but not all studies have suggested. 7,[10][11][12][13] From these findings we hypothesised that hypertension may be a trait affected by polymorphic variation in the 5-HT 2A receptor gene. A common polymorphism in the 5-HT 2A receptor, the T102C silent mutation exhibits pleiotropic effects and has been associated with a variety of complex disease traits.…”

Serotonin and Blood Pressure Regulation

“…The pathogenic effect of 5-HT was initially supported by studies reported decades ago that showed the ability of the 5-HT 2A/2C receptor antagonist ketanserin to reduce blood pressure in the human and in experimental models of hypertension (Nelson et al, 1987;Liu et al, 1991;Azzadin et al, 1995;Krygicz et al, 1996;van Schie et al, 2002), but 380 this effect was later attributed to ␣-adrenergic receptor blockade (Vanhoutte 1991;Wenting et al, 1982;Cohen et al, 1983a;Vanhoutte et al, 1988;van Zwieten et al, 1992). Other 5-HT 2A receptor antagonists such as ritanserin and 6-methyl-1-(1-methylethyl)ergoline-8â -carboxylic acid 2-hydroxy-1-methylpropyl ester (LY53857) have not proven effective in reducing blood pressure (Cohen et al, 1983b;Gradin et al, 1985;Dalton et al, 1986;Nelson et al, 1987;Frishman et al, 1988;Stott et al, 1988;Docherty, 1989), making the effect of 5-HT on blood pressure equivocal.…”

Mechanisms of action of eperisone on isolated dog saphenous arteries and veins.

“…These results may indicate that eperi sone blocks a, and a2 adrenoceptors and serotonin receptors in vascular smooth mus cle. Vascular serotonin (5-HT) receptor sub type is considered to be 5-HT2 (16,17), since ketanserin, a selective 5-HT2 antagonist with some blocking activity, attenuates the se rotonin-induced contractions in dog saphe nous arteries and veins (present study), lowers systemic blood pressure and de creases peripheral vascular resistance (17).…”