Schoemaker R G, Du X Y, Bax W A, Bos E, Saxena P R
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Netherlands.
Eur J Pharmacol. 1993 Jan 5;230(1):103-5. doi: 10.1016/0014-2999(93)90417-g.
Although 5-hydroxytryptamine (5-HT) elicits positive inotropic effects in the human isolated atrium via 5-HT4 receptors, no data are available about its effects in the ventricular myocardium. We investigated the inotropic effects of 5-HT in human healthy ventricular trabeculae and compared these effects with those in right atrial trabeculae. Baseline force of contraction as well as the response to noradrenaline, used to check inotropic responsiveness of the tissue, was significantly higher in ventricular (391 +/- 10 and 719 +/- 126 mg, respectively) than in atrial tissue (189 +/- 5 and 383 +/- 79 mg, respectively). However, 5-HT increased the force of contraction up to 309 +/- 82 mg at 10(-4) M in atrial trabeculae, but failed to affect the force of contraction in ventricular tissue. We conclude that, in contrast to atrial tissue, 5-HT is ineffective as a positive inotropic agent in human ventricular trabeculae. This finding obviously rules out the development of 5-HT4 receptor agonists for the treatment of heart failure, but suggests the absence of ventricular side-effects of 5-HT4 receptor (ant)agonists should these agents be used in the treatment of gastrointestinal disorders.
尽管5-羟色胺（5-HT）通过5-HT4受体在人离体心房中引发正性肌力作用，但关于其在心室心肌中的作用尚无数据。我们研究了5-HT对人健康心室小梁的正性肌力作用，并将这些作用与右心房小梁中的作用进行比较。用于检查组织正性肌力反应性的收缩基线力以及对去甲肾上腺素的反应，在心室中（分别为391±10和719±126mg）显著高于心房组织（分别为189±5和383±79mg）。然而，5-HT在心房小梁中以10(-4)M的浓度使收缩力增加至309±82mg，但未能影响心室组织的收缩力。我们得出结论，与心房组织不同，5-HT在人心室小梁中作为正性肌力药物无效。这一发现显然排除了开发5-HT4受体激动剂用于治疗心力衰竭的可能性，但表明如果将5-HT4受体（抗）激动剂用于治疗胃肠道疾病，可能不存在心室副作用。
