title: Cardiovascular effects of acute treatment with the antipsychotic drug olanzapine in rats.
abstract: 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.
authors: Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, 2176 Health Sciences Mall, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors: Joanne Y T
authors: JY
authors: Leung
authors: Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, 2176 Health Sciences Mall, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors: Catherine C Y
authors: CC
authors: Pang
authors: British Columbia Mental Health & Addictions Research Institute, 938 W 28th Ave., Vancouver, British Columbia V5Z 4H4, Canada.
authors: Ric M
authors: RM
authors: Procyshyn
authors: 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. Electronic address: al.barr@ubc.ca.
authors: Alasdair M
authors: AM
authors: Barr
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000633:toxicity*; D062186:Arterial Pressure / Q000187:drug effects; D001569:Benzodiazepines / Q000008:administration & dosage / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: Antipsychotic drugs; Cardiovascular; Hypotension; Olanzapine; Venous tone