Leung Joanne Y T, Pang Catherine C Y, Procyshyn Ric M, Barr Alasdair M
Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, 2176 Health Sciences Mall, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
British Columbia Mental Health & Addictions Research Institute, 938 W 28th Ave., Vancouver, British Columbia V5Z 4H4, Canada.
Vascul Pharmacol. 2014 Sep;62(3):143-9. doi: 10.1016/j.vph.2014.06.003. Epub 2014 Jun 23.
Treatment with antipsychotics is associated with adverse cardiovascular effects such as orthostatic hypotension and arrhythmias. Despite the higher prevalence of cardiovascular complications in patients with schizophrenia, the effects of antipsychotic drugs on vascular tone and cardiac contractility have received little attention. In order to better understand the cardiovascular effects of antipsychotic drugs, we investigated if the atypical antipsychotic olanzapine alters in vivo cardiovascular function in rats. Male Sprague-Dawley rats were prepared with indwelling catheters. After 4 h of recovery from surgery, the mean arterial pressure (MAP), mean circulatory filling pressure (MCFP; index of body venous tone), heart rate, left ventricular peak systolic pressure (LVP) and cardiac contractility (±dP/dt) were measured in conscious, unrestrained rats for 60 min after a single injection of olanzapine (3 or 15 mg/kg, i.p.) or vehicle. Cardiovascular measurements were not altered at any time points in the vehicle-treated rats. Olanzapine did not affect heart rate, but dose-dependently decreased MAP, MCFP, LVP and +dP/dt. Acute olanzapine treatment in rats thus reduced blood pressure and venous tone, as well as cardiac contractile function. Decreased venous tone may be a contributing factor to orthostatic hypotension commonly observed in patients during initiation of antipsychotic therapy.
使用抗精神病药物进行治疗会带来不良心血管效应，如体位性低血压和心律失常。尽管精神分裂症患者心血管并发症的患病率较高，但抗精神病药物对血管张力和心脏收缩性的影响却很少受到关注。为了更好地了解抗精神病药物的心血管效应，我们研究了非典型抗精神病药物奥氮平是否会改变大鼠的体内心血管功能。选用雄性斯普拉格-道利大鼠并植入留置导管。手术恢复4小时后，在清醒、不受约束的大鼠单次注射奥氮平（3或15mg/kg，腹腔注射）或赋形剂后60分钟，测量其平均动脉压（MAP）、平均循环充盈压（MCFP；体静脉张力指标）、心率、左心室收缩压峰值（LVP）和心脏收缩性（±dP/dt）。在接受赋形剂治疗的大鼠中，任何时间点的心血管测量值均未改变。奥氮平不影响心率，但剂量依赖性地降低MAP、MCFP、LVP和 +dP/dt。因此，大鼠急性奥氮平治疗可降低血压和静脉张力，以及心脏收缩功能。静脉张力降低可能是抗精神病治疗开始时患者常见体位性低血压的一个促成因素。
