IntroductionExogenous histamine, acting peripherally via H 1 and H 2 receptors, produces a decrease in mean arterial pressure (MAP). Similarly, administration of compound 48/80, which increases a release of endogenous histamine from mast cells, leads to circulatory depression and occurrence of ventricular arrhythmias in rats [1]. Previous studies demonstrate that plasma histamine concentrations, after injection of compound 48/80, can be lowered by pre-treatment with tricyclic antidepressants in rats [2]. Moreover, amitriptyline (AMI) and mirtazapine treatment also reduces peak plasma histamine level, which follows an intravenous (i. v.) administration of histamine in rats [3] and cats [4], respectively. In this study we examined cardiovascular responses and changes in plasma histamine concentrations after i. v. histamine injection in rats pre-treated with AMI and citalopram (CIT) which are representatives of two different classes of antidepressants.
Materials and methodsStudies were carried out in male Wistar rats anaesthetised with ethylurethane (1.25 g/kg intraperitoneally [i. p.]) weighing 230 -260 g in accordance with EU directives. Arterial pressure and heart rate (HR) were measured using the pressure transducer RMN-201 (Temed, Inflamm. res. 53, Supplement 1 (2004) S97-S98 Poland) and the electrocardiograph Diascope 2 (Unitra Biazet, Poland), respectively [5,6]. The animals (n = 6) were treated i. v. with histamine (10 mg/kg) 15 min or 1 h after i.p. pre-treatment with AMI (2.7 mg/kg), CIT (1 mg/kg) or saline (0.5 ml). In the control groups, the rats were treated with saline (0.5 ml i. v.). The animals were monitored continuously for 2 h. Body temperature was maintained at 36.5 -37.5°C using a heating lamp throughout the experiment. All the studies were performed between 8.00 and 12.00.In a parallel study rats (n = 5 to 10) were treated as described above, and plasma histamine concentrations were measured spectrofluorometrically. Blood was collected from the right carotid artery before histamine injection and 2 and 4 min afterwards. Plasma was prepared as described previously [7].
Results and discussionThere were no differences in initial (before pre-treatment) MAP, pulse pressure (PP) and HR between the groups, the values being 86.63 ± 4.61 mmHg, 35.67 ± 7.08 mmHg and 346 ± 12 beats/min, respectively. In the saline pre-treated group, bolus injection of histamine transiently decreased MAP and PP by 47.25 % and 59.23 %, respectively, with no influence on HR.Pre-treatment with AM and CIT (given 15 min or 1 h before histamine) reduced histamine-induced influence on MAP and PP, and this effect was greater in AMI-than in CITtreated group (Table 1). There were no differences between Table 1. Basal (before treatment) and minimal mean arterial pressure (MAP) and pulse pressure (PP) values after histamine (10 mg/kg i. v.) injection and pre-treatment with amitriptyline (AMI; 2.7 mg/kg) and citalopram (CIT; 1 mg/kg) in rats. Results are mean ± SD; six animals per group; * p < 0.05 vs. saline-pre-treated histamine-injec...
