Effect of losartan and enalapril on cognitive deficit caused by Goldblatt induced hypertension.
The present study was designed to evaluate the learning and memory, in an altered physiological state associated with increased blood pressure and activated renin angiotensin system in Wistar rats. The role of angiotensin in cognitive function was assessed by treatment with angiotensin converting enzyme (ACE) inhibitor enalapril (2 mg/kg), angiotensin 1 receptor (AT(1)) antagonist losartan (5 mg/kg) and their combination. The experimental renal hypertension was induced by the method of Goldblatt. Learning and memory was assessed using the radial arm maze test. Acetylcholine esterase (AChE) levels in the pons medulla, hippocampus, striatum and frontal cortex were measured as a cholinergic marker of learning and memory. Results indicate that in comparison to normotensive rats, renal hypertensive rats committed significantly higher number of errors and took more trials and days to learn the radial arm maze learning and exhibited memory deficit in the radial arm maze retrieval after two weeks of retention interval, indicating impaired acquisition and memory. Treatment with enalapril, losartan and their combination attenuated the observed memory deficits indicating a possible role of renin angiotensin system in cognitive function. AChE level was reduced in hippocampus and frontal cortex of renal hypertensive rats which could be attributed to the observed memory deficit in hypertensive rats. It can be concluded that, renal hypertensive rats had a poor acquisition, retrieval of the learned behavior, perhaps a possible disturbance in memory consolidation process and that this state was reversed with ACE inhibitor enalapril and AT 1 receptor antagonist losartan.
Srinivasan
J
J
Neuropharmacology Laboratory, Department of Pharmacology, J.S.S. College of Pharmacy, Ootacamund 643 001, India.
Jayadev
S
S
Kumaran
D
D
Ahamed
K F Haja Nazeer
KF
Suresh
B
B
Ramanathan
M
M
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004656:Enalapril / Q000494:pharmacology*; D006801:Humans; D006978:Hypertension, Renovascular / Q000150:complications* / Q000188:drug therapy*; D007858:Learning / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System; D013997:Time Factors
D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D004656:Enalapril; D000110:Acetylcholinesterase; D019808:Losartan