Effect of ivabradine, captopril and melatonin on the behaviour of rats in L-nitro-arginine methyl ester-induced hypertension

J Physiol Pharmacol. 2016 Dec;67(6):895-902.

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.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Behavior, Animal / drug effects*
  • Benzazepines / pharmacology*
  • Blood Pressure / drug effects
  • Captopril / pharmacology*
  • Heart Rate / drug effects
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Ivabradine
  • Locomotion / drug effects
  • Male
  • Melatonin / pharmacology*
  • NG-Nitroarginine Methyl Ester / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzazepines
  • Nitric Oxide
  • Ivabradine
  • Captopril
  • Nitric Oxide Synthase
  • Melatonin
  • NG-Nitroarginine Methyl Ester