Ivabradine does not impair anxiety-like behavior and memory in both healthy and L-NAME-induced hypertensive rats

• Published in: Physiological research Vol. 67; no. Supplementum 4; pp. S655 - S664
• Main Authors: Krajcirovicova, K, Aziriova, S, Baka, T, Repova, K, Adamcova, M, Paulis, L, Simko, F
• Format: Journal Article
• Language: English
• Published: Czech Republic Institute of Physiology 01.01.2018
• Subjects: Animals; Anxiety; Anxiety - physiopathology; Arginine; Behavior; Blood pressure; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiovascular disease; Cognitive ability; Coronary vessels; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Heart failure; Heart rate; Heart Rate - drug effects; Heart Rate - physiology; Hyperpolarization; Hypertension; Hypertension - chemically induced; Hypertension - drug therapy; Hypertension - physiopathology; Investigations; Ion channels (cyclic nucleotide-gated); Ivabradine - pharmacology; Ivabradine - therapeutic use; Laboratory animals; Learning; Light; Locomotion; Male; Melatonin; Memory - drug effects; Memory - physiology; Mortality; NG-Nitroarginine methyl ester; NG-Nitroarginine Methyl Ester - toxicity; Nitric oxide; Rats; Rats, Wistar; Rodents; Stress; Slovakia
• ISSN: 0862-8408; 1802-9973
• DOI: 10.33549/physiolres.934048

Cardiovascular pathologies are frequently associated with anxiety and other behavioral disturbances. Ivabradine, an inhibitor of the hyperpolarization-activated cyclic nucleotide-gated channels in the sinoatrial node, decreases heart rate and provides cardiovascular protection. Although ivabradine is increasingly used in cardiovascular medicine, the data on its behavioral effects are lacking. The aim of this work was to show ivabradine's potential effect on behavior in healthy and hypertensive rats. After a four-week treatment period, systolic blood pressure was increased in the N(G)-nitro-L-arginine methyl ester (L-NAME)-group and ivabradine significantly reduced it. Furthermore, it reduced the heart rate in both the control and L-NAME-group. In the control group, ivabradine enhanced the time spent in and transition to the open arms of the elevated plus maze test (EPM). In the L-NAME-group, ivabradine does not show a significant effect on the time spent in the EPM open arms and the number of transitions into them. Furthermore, ivabradine has no impact on cognitive function in both control and L-NAME groups. We conclude that ivabradine showed no undesirable effects on anxiety, locomotion or learning; in fact, some of these parameters were even improved. For the first time it has been shown that ivabradine is a safe cardiovascular drug regarding its effect on psycho-behavioral manifestations.