Amlodipine limits microglia activation and cognitive dysfunction in aged hypertensive mice

J Hypertens. 2023 Jul 1;41(7):1159-1167. doi: 10.1097/HJH.0000000000003445. Epub 2023 Apr 5.


Background: SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause for stroke and dementia. Calcium-channel blockers are known to reduce blood pressure variability and may thus offer benefit against dementia. Beyond this effect, the impact of calcium-channel blockers on hypertension-induced neuroinflammation, and especially, microglial phenotype remains unknown. We aimed to study the ability of amlopidine to alleviate microglia inflammation, and slow down cognitive dysfunction in aged hypertensive mice.

Methods: Hypertensive BPH/2J and normotensive BPN/3J mice were studied until 12 months of age. Hypertensive mice were untreated or received amlodipine (10 mg/kg per day). Blood pressure parameters were measured by telemetry and tail cuff plethysmography. Mice underwent repeated series of cognitive tasks. Brain immunohistochemistry was performed to study blood-brain barrier dysfunction and microglial pro-inflammatory phenotype (CD68 + Iba1 + cells; morphological analysis).

Results: Amlodipine normalized SBP over the entire life span and decreased blood pressure variability. BPH/2J mice exhibited impaired short-term memory that was prevented by amlodipine at 12 months (discrimination index 0.41 ± 0.25 in amlodipine-treated vs. 0.14 ± 0.15 in untreated BPH/2J mice, P = 0.02). Amlopidine treatment of BPH/2J did not prevent blood-brain barrier leakage, a measure of cerebral small vessel disease, but limited its size. Microglia's inflammatory phenotype in BPH/2J, characterized by an increased number of Iba1 + CD68 + cells, increased soma size and shortened processes, was partly reduced by amlodipine.

Conclusion: Amlodipine attenuated the short-term memory impairment in aged hypertensive mice. Beyond its blood pressure lowering capacity, amlodipine may be cerebroprotective by modulating neuroinflammation.

MeSH terms

  • Amlodipine / pharmacology
  • Amlodipine / therapeutic use
  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / physiology
  • Calcium
  • Calcium Channel Blockers / therapeutic use
  • Dementia*
  • Humans
  • Hypertension* / complications
  • Hypertension* / drug therapy
  • Hypertension* / genetics
  • Male
  • Mice
  • Microglia
  • Neuroinflammatory Diseases
  • Prostatic Hyperplasia* / drug therapy


  • Amlodipine
  • Calcium
  • Calcium Channel Blockers
  • Antihypertensive Agents