Pharmacological inhibition of inducible nitric oxide synthase (iNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, convalesce behavior and biochemistry of hypertension induced vascular dementia in rats

• Published in: Pharmacology, biochemistry and behavior Vol. 103; no. 4; pp. 821 - 830
• Main Authors: Sharma, Bhupesh, Singh, Nirmal
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2013
• Subjects: 4′-hydroxy-3′-methoxyacetophenone; Acetophenones - pharmacology; Acetophenones - therapeutic use; Aminoguanidine; Animals; Brain Chemistry - drug effects; Brain Chemistry - physiology; Convalescence; Dementia, Vascular - drug therapy; Dementia, Vascular - enzymology; Dementia, Vascular - etiology; DOCA salt; Guanidines - pharmacology; Guanidines - therapeutic use; Hypertension - complications; Hypertension - drug therapy; Hypertension - enzymology; iNOS; Male; Maze Learning - drug effects; Maze Learning - physiology; Mean arterial blood pressure; Morris water maze; NADPH oxidase; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; Rats; Rats, Wistar; Vascular dementia; 4′-hydroxy-3′-methoxyacetophenone; Aminoguanidine; DOCA salt; Morris water maze; Vascular dementia; Mean arterial blood pressure; NADPH oxidase; iNOS
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2012.11.011

Cognitive disorders are likely to increase over the coming years (5–10). Vascular dementia (VaD) has heterogeneous pathology and is a challenge for clinicians. Current Alzheimer's disease drugs have had limited clinical efficacy in treating VaD and none have been approved by major regulatory authorities specifically for this disease. Role of iNOS and NADPH-oxidase has been reported in various pathological conditions but there role in hypertension (Hypt) induced VaD is still unclear. This research work investigates the salutiferous effect of aminoguanidine (AG), an iNOS inhibitor and 4′-hydroxy-3′-methoxyacetophenone (HMAP), a NADPH oxidase inhibitor in Hypt induced VaD in rats. Deoxycorticosterone acetate-salt (DOCA-S) hypertension has been used for development of VaD in rats. Morris water-maze was used for testing learning and memory. Vascular system assessment was done by testing endothelial function. Mean arterial blood pressure (MABP), oxidative stress [aortic superoxide anion, serum and brain thiobarbituric acid reactive species (TBARS) and brain glutathione (GSH)], nitric oxide levels (serum nitrite/nitrate) and cholinergic activity (brain acetyl cholinesterase activity-AChE) were also measured. DOCA-S treated rats have shown increased MABP with impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate & brain GSH levels along with increase in serum & brain TBARS, and brain AChE activity. AG as well as HMAP significantly convalesce Hypt induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that AG, an iNOS inhibitor and HMAP, a NADPH-oxidase inhibitor may be considered as potential agents for the management of Hypt induced VaD.
► DOCA-salt hypertension (Hypt) has induced endothelial dysfunction (Edf) & dementia. ► DOCA-salt has increased MABP, oxidative stress, AChE activity & decreased NO. ► Inhibitors of NADPH-oxidase & iNOS have attenuated Hypt induced Edf & dementia. ► Both the inhibitors have attenuated Hypt induced biochemical impairments. ► Inhibitor of NADPH-oxidase & iNOS have shown good potential in vascular dementia.