Original Investigation

Psychopharmacology

, Volume 223, Issue 3, pp 307-317

Defensive effect of natrium diethyldithiocarbamate trihydrate (NDDCT) and lisinopril in DOCA–salt hypertension-induced vascular dementia in rats

  • Bhupesh SharmaAffiliated withPharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University
  • , Nirmal SinghAffiliated withPharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University Email author 

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Abstract

Rationale

Vascular dementia and hypertension are increasing day by day, with a high degree of co-occurrence. Tremendous amount of research work is required so that new pharmacological agents may be identified for their appropriate therapeutic utility to combat different dementing disorders.

Objectives

This study investigates the effect of natrium diethyldithiocarbamate trihydrate (NDDCT), a nuclear factor kappa-B (NF-κB) inhibitor, as well as lisinopril, an angiotensin converting enzyme (ACE) inhibitor, on deoxycorticosterone acetate (DOCA) hypertension-induced vascular dementia in rats.

Methods

DOCA was used to induce hypertension and associated vascular dementia. Morris water maze (MWM) was used for testing learning and memory. Endothelial function was assessed by acetylcholine-induced endothelium-dependent relaxation of aortic strips. Different biochemical estimations were used to assess oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, and brain glutathione), nitric oxide levels (serum nitrite/nitrate), and cholinergic activity (brain acetyl cholinesterase activity).

Results

DOCA treatment significantly raised the mean arterial blood pressure of rats, and these hypertensive rats performed poorly on MWM, reflecting impairment of learning and memory. DOCA treatment also impaired vascular endothelial function and different biochemical parameters. Treatments of NDDCT as well as lisinopril significantly attenuated DOCA hypertension-induced impairment of learning and memory, endothelial dysfunction, and changes in various biochemical levels.

Conclusions

DOCA–salt hypertension induces vascular dementia in rats. NF-κB as well as ACE inhibitors may be considered as potential pharmacological agents for the management of hypertension-induced vascular dementia.

Keywords

Nuclear factor kappa-B Angiotensin converting enzyme Endothelial dysfunction Morris water maze Alzheimer’s disease Oxidative stress