title: 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.
abstract: 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.
authors.affiliation: CNS and CVS Research Lab., Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala 147002, Punjab, India. bhupeshresearch@gmail.com
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Sharma
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
mesh_terms: D000098:Acetophenones / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D003289:Convalescence; D015140:Dementia, Vascular / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000098:Acetophenones; D006146:Guanidines; C056165:acetovanillone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019255:NADPH Oxidases; C004479:pimagedine