Amitriptyline and citalopram inhibit histamine-induced cardiovascular effects in rats

Abstract

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...

Inhibition of mast cell degranulation-induced drop of blood pressure with clemastine, cromolyn and compound 48/80 pretreatment

“…In agreement with the previous studies [2,4], compound 48/80-induced mast cell degranulation resulted in a sudden drop of MAP immediately after intravenous administration (Fig. 1).…”

Influence of centrally acting amitriptyline and citalopram on histamine-induced cardiovascular effects in rats

“…However, these effects were signifi cantly lower in comparison to those obtained after peripheral injection of both antidepressants [3]. Additionally, we showed that both agents were able to alter the reactivity of the cardiovascular centre to hypotensive stimuli, since the depressor effect elicited by histamine was accompanied by tachycardia, probably refl ex-mediated.…”

“…Moreover, amitriptyline (AMI) and citalopram (CIT) reduce an increase of plasma histamine levels after an intravenous (i.v.) bolus injection [2], and this action is accompanied by inhibition of histamine-induced decreases in mean arterial pressure (MAP) and pulse pressure (PP), without infl uence on heart rate (HR) [3]. We suggested that the reduction of increase of free histamine levels in plasma may possibly result from changes in histamine binding or uptake due to modulation of structure of cellular membranes [3].…”

Influence of amitriptyline on central histamine-induced reversal of haemorrhagic shock in rats

“…The effect is due to activation of the sympathetic nervous system [2], the renin-angiotensin system [3] and secretion of arginine vasopressin [4] and proopiomelanocortin-derived peptides [5]. However, our previous studies have demonstrated that the tricyclic antidepressant amitriptyline (AMI) which inhibits serotonin and noradrenaline re-uptake affected, both centrally and peripherally, vascular resistance regulatory mechanisms in intravenous histamine-induced hypotension in rats [6,7]. Thus, the aim of this study was to examine a possible infl uence of AMI on central histamine-evoked resuscitating effect in haemorrhage-shocked rats.…”