Wenting G J, Brouwer R M, vd Meiracker A J, Man in't Veld A J, Schalekamp M A
Department of Internal Medicine I, University Hospital Rotterdam Dijkzigt, The Netherlands.
Acta Cardiol. 1987;42(5):339-54.
It remains to be established whether ketanserin's antihypertensive effect is caused by blockade of serotonergic type 2 receptors (S2), by blockade of alpha 1-adrenoceptors or by combined effect on both receptors. We therefore performed several clinical studies. Ketanserin, 10 mg i.v., lowered blood pressure in 6 patients with essential hypertension and blocked, at the same time, the contraction of hand veins to exogenous serotonin. In contrast, ketanserin had no effect on the venoconstrictor action of noradrenaline. Ketanserin also did not alter the pressor effect of bolus injections of the alpha 1-agonist phenylephrine. Furthermore, ketanserin had a distinct hypotensive effect in 4 normotensive patients with autonomic insufficiency who were unresponsive to alpha 1-adrenoceptor blockade. Moreover, the ketanserin-induced marked increase in digital blood flow in 7 patients with Raynaud's phenomenon was not blocked by pretreatment with high doses of the alpha 1-adrenoceptor blockade. However, in patients with essential hypertension, the antihypertensive effect of ketanserin was blunted by pretreatment with prazosin. This may be related to S2 blockade of the alleged amplifying effect of serotonin on alpha 1-adrenoceptor mediated vasoconstriction but the data do not exclude concomitant alpha-blockade by ketanserin. We conclude that the mechanism of ketanserin's antihypertensive effect requires further clarification; nevertheless the data cited above do not support the view that ketanserin is nothing more than another alpha-blocker.
酮色林的降压作用是由5-羟色胺能2型受体（S2）阻断、α1-肾上腺素能受体阻断还是对两种受体的联合作用引起，仍有待确定。因此，我们进行了多项临床研究。静脉注射10毫克酮色林可使6例原发性高血压患者的血压降低，同时阻断手部静脉对外源性5-羟色胺的收缩反应。相比之下，酮色林对去甲肾上腺素的静脉收缩作用没有影响。酮色林也不会改变单次注射α1-激动剂去氧肾上腺素的升压作用。此外，酮色林对4例自主神经功能不全的血压正常患者有明显的降压作用，这些患者对α1-肾上腺素能受体阻断无反应。此外，高剂量的α1-肾上腺素能受体阻断预处理并不能阻断酮色林引起的7例雷诺现象患者手指血流量的显著增加。然而，在原发性高血压患者中，哌唑嗪预处理会减弱酮色林的降压作用。这可能与5-羟色胺对α1-肾上腺素能受体介导的血管收缩的所谓放大作用的S2阻断有关，但这些数据并不排除酮色林同时存在α阻断作用。我们得出结论，酮色林降压作用的机制需要进一步阐明；然而，上述数据并不支持酮色林仅仅是另一种α阻断剂的观点。
