title: Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function.
abstract: BACKGROUND
  Inhibition of renin-angiotensin system (RAS) improves cognitive functions in hypertensive patients. However, role of AT1 and AT2 receptors in memory impairment due to cholinergic hypofunction is unexplored.
  
  
  OBJECTIVE
  This study investigated the role of AT1 and AT2 receptors in cerebral blood flow (CBF), cholinergic neurotransmission, and cerebral energy metabolism in scopolamine-induced amnesic mice.
  
  
  METHODS
  Scopolamine was given to male Swiss albino mice to induce memory impairment tested in passive avoidance and Morris water maze tests after a week long administration of blocker of AT1 receptor, candesartan, and AT2 receptor, PD123, 319. CBF was measured by laser Doppler flowmetry. Biochemical and molecular studies were done in cortex and hippocampus of mice brain.
  
  
  RESULTS
  Scopolamine caused memory impairment, reduced CBF, acetylcholine (ACh) level, elevated acetylcholinesterase (AChE) activity, and malondialdehyde (MDA). Administration of vehicle had no significant effect on any parameter in comparison to control. Candesartan prevented scopolamine-induced amnesia, restored CBF and ACh level, and decreased AChE activity and MDA level. In contrast, PD123, 319 was not effective. However, the effect of AT1 receptor blocker on memory, CBF, ACh level, and oxidative stress was blunted by concomitant blockade of AT2 receptor. Angiotensin-converting enzyme (ACE) activity, ATP level, and mRNA expression of AT1, AT2, and ACE remained unaltered.
  
  
  CONCLUSIONS
  The study suggests that activation of AT1 receptors appears to be involved in the scopolamine-induced amnesia and that AT2 receptors contribute to the beneficial effects of candesartan. Theses finding corroborated the number of clinical studies that RAS inhibition in hypertensive patients could be neuroprotective.
authors.affiliation: Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Santoshkumar
authors.initials: S
authors.lastname: Tota
authors.forename: Kashif
authors.initials: K
authors.lastname: Hanif
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Kamat
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
authors.forename: Chandishwar
authors.initials: C
authors.lastname: Nath
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D018727:Muscarinic Antagonists / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000378:metabolism*; D012601:Scopolamine / Q000633:toxicity*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D018727:Muscarinic Antagonists; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; C073402:PD 123319; D012601:Scopolamine; C081643:candesartan