title: Effect of ivabradine, captopril and melatonin on the behaviour of rats in L-nitro-arginine methyl ester-induced hypertension.
abstract: Cardiovascular diseases including hypertension are often associated with behavioural alterations. The aim of this study was to show, whether ivabradine, the blocker of If-channel in sinoatrial node, is able to modify the behaviour of rats in L-nitro-arginine methyl ester (L-NAME)-induced hypertension and to compare the effect of ivabradine with captopril and melatonin. 12-week-old male Wistar rats were divided into the following groups: controls, ivabradine (10 mg/kg/24 h), L-NAME (40 mg/kg/24 h), L-NAME + ivabradine, L-NAME + captopril (100 mg/kg/24 h), L-NAME + melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff method once a week. The behaviour of rats was investigated during 23-hours in the phenotyper after four weeks of the treatment. Chronic administration of L-NAME induced hypertension without a change in HR. All tested substances partly prevented the increase of SBP, while ivabradine and melatonin also reduced HR. Ivabradine, captopril and melatonin reduced daily food intake, slightly decreased daily water intake and attenuated body weight gain. In L-NAME group, locomotor activity was enhanced by ivabradine, whereas exploratory behaviour was increased by melatonin and captopril. In conclusion, ivabradine, besides its potentially protective hemodynamic actions, does not seem to exert any disturbing effects on behaviour in L-NAME-induced hypertension in rats, while some of its effects were similar to captopril or melatonin. It is suggested that ivabradine used in cardiovascular indications is harmless regarding the effect on behaviour.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: S
authors.initials: S
authors.lastname: Aziriova
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: K
authors.initials: K
authors.lastname: Repova
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: K
authors.initials: K
authors.lastname: Krajcirovicova
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: T
authors.initials: T
authors.lastname: Baka
authors.affiliation: Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: S
authors.initials: S
authors.lastname: Zorad
authors.affiliation: 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: V
authors.initials: V
authors.lastname: Mojto
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: P
authors.initials: P
authors.lastname: Slavkovsky
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: J
authors.initials: J
authors.lastname: Hodosy
authors.affiliation: Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Adamcova
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.|Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: L
authors.initials: L
authors.lastname: Paulis
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic. fedor.simko@fmed.uniba.sk.|Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic.|3rd Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: F
authors.initials: F
authors.lastname: Simko
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D000077550:Ivabradine; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D009569:Nitric Oxide; D000077550:Ivabradine; D002216:Captopril; D019001:Nitric Oxide Synthase; D008550:Melatonin; D019331:NG-Nitroarginine Methyl Ester