KETANSERINS SYMPATHOLYTIC AND SEROTONIN2-RECEPTOR BLOCKING ACTIONS PRECEDE THE HYPOTENSIVE EFFECTS

The hypotensive action of ketanserin in humans remains incompletely de fined but may be mediated by factors unrelated to vascular alpha, or s erotonin2-receptor blockade. We examined the effects of ketanserin on indices of sympathetic drive, alpha1- and serotonin2-receptor response s, and sympathetic tone in 13 elderly men with mild hypertension. Stud ies were performed after ten days and six weeks of double-blind assign ment to placebo and ketanserin 40 mg twice daily. An eight week long s ingle-blind, placebo washout period separated the double-blind phases. In the entire group, ketanserin lowered BP and heart rate significant ly after six weeks but not at ten days. In contrast, plasma noradrenal ine, an index of sympathetic drive, and platelet aggregation in respon se to 1 muM serotonin, an index of serotonin2-receptor antagonism, dec lined significantly after both ten days and six weeks (P < 0.05) on ke tanserin versus placebo. Mean BP after six weeks on ketanserin fell to > 10% in seven patients (responders) and to < 10% in six subjects non responders). Responders had higher baseline SBPs and heart rates compa red with nonresponders. Even in responders, BP was reduced at six week s but not after ten days on ketanserin versus placebo. Plasma and plat elet noradrenaline, plasma renin activity, and platelet responses to s ertonin at baseline and during ketanserin did not distinguish between responders and nonresponders. Ketanserin reduces sympathetic drive and antagonizes serotonin2-receptors in the short term. The relationship of these actions to the hypotensive effect of ketanserin, which is del ayed and dependent on the initial BP, is unclear.