DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20183501

The study of effects of inhibition of the renin angiotensin system on memory in rats

Medhinee Kulkarni, Prasad Pandit, Kiran Bhave

Abstract


Background: The existence of an independent renin angiotensin aldosterone system (RAAS) has been well-established and is known to modulate various pathological processes such as neuroinflammation, neurodegeneration, and neural injury, in addition to the RAAS in the cardiovascular system.

Methods: Eighteen Wistar rats were divided into 3 study groups (n=6; Losartan, Ramipril, Normal Saline), trained on the Cook’s Pole climbing apparatus till the conditioned avoidance response (CAR) rate was 100%. The retention of CAR was tested each week for 4 consecutive weeks. The number of times that the animal successfully avoided the shock, and the time taken for this avoidance were measured and compared with placebo (Normal Saline). The values have been expressed as Mean±Standard Deviation (SD). A p-value of less than 0.05 has been considered as significant.

Results: The retention of the conditioned avoidance response in the group receiving study drugs was significantly more than the placebo group. However, there was no show significant difference between Losartan and Ramipril in the rate of retention, or the time taken for avoidance.

Conclusions: In this study, Ramipril and Losartan have a beneficial effect on learning and memory as compared to plcebo.


Keywords


Cook’s Pole-Climbing apparatus, Cognition, Losartan, Memory, RAS inhibitors, Ramipril

Full Text:

PDF

References


von Bohlen und Halbach O, Albrecht D. The CNS renin-angiotensin system. Cell Tissue Res. 2006 Nov;326(2):599-616.

Fogari R, Zoppi A. Effect of antihypertensive agents on quality of life in the elderly. Drugs and Aging. 2004;21(6):377-93.

Fletcher A. Quality of life in the management of hypertension. Clin Exp Hypertens. 1999 Jul-Aug;21(5-6):961-72.

Wright JW, Harding JW. The brain RAS and Alzheimer's disease. Exp Neurol. 2010 Jun;223(2):326-33.

Mogi M, Horiuchi M. Effects of angiotensin II receptor blockers on dementia. Hypertens Res. 2009 Sep; 32(9):738-40.

Li NC, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, et al. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ. 2010 Jan 12; 340:b5465.

Mogi M, Iwanami J, Horiuchi M. Roles of Brain Angiotensin II in Cognitive Function and Dementia. Int J Hypertens. 2012;201(2):169649.

Albrecht D. Physiological and pathophysiological functions of different angiotensins in the brain. Bri J Pharmacol. 2010;159(7):1392-401.

Kotchen TA. Hypertension in Harrison’s Principles of Internal Medicine Longo, Fauci, Kasper, Hauser, Jameson and Loscalzo (Ed.) 18th Ed;, McGraw Hill Publications; 2012:2042-2059.

Sreemantula S, Nammi S, Kolanukonda R, Koppula S, Boini KM. Adaptogenic and nootropic activities of aqueous extract of Vitisvinifera (grape seed): an experimental study in rat model; BMC Complementary and Alternative Medicine. January 2005:5:1.

Barrett KE, Barman SM, Boitano S, Brooks HL. Learning, Memory, Speech and Language in Ganong’s Review of Medical Physiology 23rd Ed., Tata McGraw Hill publications; 289-300.

Bild W, Hritcu L, Stephanescu C, Ciobica A. Inhibition of Central Angiotensin II Enhances Memory Function and Reduces Oxidative Stress Status in Rat Hippocampus; Progress in Neuropsycho pharmacology and Biological Psychiatry. June 2013;43(3):79-88.

Raghavendra V, Chopra K, Kulkarni SK. Comparative effects of Captopril and Losartan on Memory Enhancing effects using Inhibitory Shock Avoidance Paradigm in mice; Neuropeptides. Feb 2001;35(1):65-9.

Basso N, Paglia N, Stella I, deCavanaugh EM. Protective Effects of RAS on Aging; Regulatory Peptides. June 2005;128(3):247-52.

Kume K, Hanyu H, Sakurai H. Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease; Geriatrics and Gerontology International. 2011 Sep 19.

Wang J, Ho L, Chen L, Zhao Z, Zhao W, Qian X, et al. Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease. The J Clin Investiga. 2007 Nov 1;117(11):3393-402.

Tian M, Zhu D, Xie W, Shi J. Central Angiotensin II induced Alzheimer’s disease-like tau phosphorylation in normal rat brains. FEBS Letters, Oct 2012;586(20):3737-46.

Tchekalarova J, Albrecht D. Angiotensin-II suppresses Long term potentiation in lateral amygdala of mice via L-type Calcium channels; Neuroscience letters. Mar 2007;415(1):68-72.

Wharton W, Stein JH, Korcarz C, Sachs J, Olson SR, Zetterberg H, et al. The effects of ramipril in individuals at risk for Alzheimer's disease: results of a pilot clinical trial. J Alzheimer's Disease. 2012 Jan 1;32(1):147-56.

Justin A, Sathishkumar M, Sudheer A, Shanthakumari S, Ramanathan M. Non-hypotensive dose of telmisartan and nimodipine produced synergistic neuroprotective effect in cerebral ischemic model by attenuating brain cytokine levels. Pharmacology Biochemistry and Behavior. 2014 Jul 1;122:61-73.

Yamada K, Horita T, Takayama M. Effect of a centrally active angiotensin converting enzyme inhibitor, perindopril, on cognitive performance in chronic cerebral hypo-perfusion rats; Brain Res. 2011 Nov 3;1421:110-20.

Dong YF, Kataoka K, Tokutomi Y. Perindopril, a centrally active angiotensin-converting enzyme inhibitor, prevents cognitive impairment in mouse models of Alzheimer's disease. FASEB J. 2011 Sep;25(9):2911-20. E-pub 2011 May 18.

Sengupta P. The Laboratory Rat: Relating Its Age with Humans Int J Prev Medic. 2013;4(6):624-30.