Anti-stress and nootropic activity of drugs affecting the renin-angiotensin system in rats based on indirect biochemical evidence.
BACKGROUND
Various stress hormones are responsible for bringing out stress-related changes and are implicated in learning and memory processes. The extensive clinical experience of angiotensin receptor blockers (ARBs) and direct renin inhibitor as antihypertensive agents provides anecdotal evidence of improvements in cognition. The neurochemical basis underlying the anti-stress and nootropic effects are unclear. This study was aimed to determine the effects of aliskiren, valsartan and their combination on the neuromediators of the central nervous system (CNS) and periphery as well as on cognitive function.


METHODS
Groups of rats were subjected to a forced swim stress for one hour after daily treatment with aliskiren, valsartan and their combination. The 24 h urinary excretion of vanillylmandellic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA), 6-β-hydroxycortisol (6-β-OH) cortisol and homovanillic acid (HVA) was determined in all groups under normal and stressed conditions. Nootropic activity was studied using cook's pole climbing apparatus and acetylcholinesterase (AChE) inhibitory activity by Ellman's method.


RESULTS
Administration of aliskiren (10 mg/kg), valsartan (20 mg/kg) and their combination at a dose of 5 and 10 mg/kg respectively reduced the urinary metabolite levels. Further, all drugs showed significant improvement in scopolamine-impaired performance and produced inhibition of the AChE enzyme.


CONCLUSIONS
The present study provides scientific support for the anti-stress and nootropic activities of aliskiren, valsartan and their combination.
Department of Pharmacology, Visveswarapura Institute of Pharmaceutical Sciences, India anilkumargcp@rediffmail.com.
K V
KV
Anil Kumar
Department of Pharmacology, Visveswarapura Institute of Pharmaceutical Sciences, India.
Shrasti
S
Nagwar
Department of Biotechnology, Government Science College, India.
Rama
R
Thyloor
Department of Pharmacology, A U college of Pharmaceutical Sciences, Andhra University, India.
Sreemantula
S
Satyanarayana
D000110:Acetylcholinesterase / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005650:Fumarates / Q000494:pharmacology; D006719:Homovanillic Acid / Q000652:urine; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D055442:Metabolome / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013312:Stress, Physiological / Q000187:drug effects*; D000068756:Valsartan / Q000494:pharmacology; D014642:Vanilmandelic Acid / Q000652:urine
D000577:Amides; D005650:Fumarates; D018697:Nootropic Agents; C446481:aliskiren; C001380:6 beta-hydroxycortisol; D006897:Hydroxyindoleacetic Acid; D014642:Vanilmandelic Acid; D000068756:Valsartan; D000110:Acetylcholinesterase; D006854:Hydrocortisone; D006719:Homovanillic Acid
Aliskiren; acetylcholinesterase; biogenic amines; cognition; renin-angiotensin system; urinary metabolites; valsartan