Scalbert E, Richer C, Giudicelli J F
Département de Pharmacologie, Faculté de Médecine, Le Kremlin-Bicêtre, France.
Fundam Clin Pharmacol. 1988;2(4):295-9. doi: 10.1111/j.1472-8206.1988.tb00641.x.
The potential cardiac presynaptic effects of ketanserin (K) (0.01-3.00 mg/kg IV) were investigated in pithed SHR in 4 experimental conditions: (a) basal heart rate (HR); (b) HR increased by selective cardiac sympathetic stimulation (SS); (c) HR increased by aminophylline infusion; and (d) HR increased by SS and brought back to basal value by clonidine. Control groups were treated with saline. In the 4 types of experiments, K, starting from 0.3 mg/kg, induced almost identical and dose-dependent decreases in HR (maximal reduction: 45 beats/(min at 3 mg/kg). Thus we conclude: (1) that K is devoid of any presynaptic facilitatory effect on norepinephrine release since it was unable to raise HR in experiment D; (2) that K is devoid of any presynaptic inhibitory effect on norepinephrine release since it lowered HR to the same extent in both experiments B (noradrenergic tachycardia) and (non-noradrenergic tachycardia); and C (3) that the bradycardia which was induced by high doses of K (much above those required to block 5-HT2 and alpha 1-adrenergic receptors) and which was of similar magnitude in the 4 experimental conditions is probably due to a direct, nonspecific depressant effect of K on the sinus node.
在4种实验条件下，对脊髓横断的自发性高血压大鼠（SHR）研究了酮色林（K）（0.01 - 3.00 mg/kg静脉注射）潜在的心脏突触前效应：（a）基础心率（HR）；（b）通过选择性心脏交感神经刺激（SS）使HR升高；（c）通过氨茶碱输注使HR升高；（d）通过SS使HR升高，然后用可乐定使其恢复到基础值。对照组用生理盐水处理。在这4种类型的实验中，从0.3 mg/kg开始，K可引起几乎相同且剂量依赖性的HR降低（最大降低幅度：3 mg/kg时为45次/分钟）。因此，我们得出以下结论：（1）K对去甲肾上腺素释放没有任何突触前促进作用，因为在实验D中它无法使HR升高；（2）K对去甲肾上腺素释放没有任何突触前抑制作用，因为在实验B（去甲肾上腺素能性心动过速）和实验C（非去甲肾上腺素能性心动过速）中它使HR降低的程度相同；（3）高剂量K（远高于阻断5-HT2和α1 - 肾上腺素能受体所需的剂量）所诱导的心动过缓，在4种实验条件下幅度相似，可能是由于K对窦房结有直接的、非特异性的抑制作用。
