B.M. Sharma, Bhupesh Sharma
firstname.lastname@example.org , email@example.com
B.M. Sharma1, Bhupesh Sharma2,3*
1 Department of Pharmacology, School of Pharmacy, BIT, Meerut, India.
2 Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, India.
3CNS and CVS Pharmacology, Conscience Research, Delhi, India.
Volume - 14,
Issue - 12,
Year - 2021
Objective: Cerebrovascular and cardiovascular disease are considered as a major risk factor for the development of VaD. This study investigates the efficacy of nicergoline in 2K1C induced vascular endothelium dysfunction and related dementia. Methods: 2K1C renovascular hypertension has induced hypertension in Albino Wistar rats (male, 200-250g). Morris water maze (MWM), and attentional set shifting tests (ASST) were used to assess the spatial learning, memory, reversal learning, and executive functioning in animals. Mean artery blood pressure, serum nitrite/nitrate, vascular endothelial function, aortic superoxide anion, brains’ oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), inflammatory markers (myeloperoxidase-MPO), calcium levels, acetylcholinesterase activity-and AChE ativity were also assessed. Nicergoline (5 mg/kg or 10 mg/kg p.o.) was used as the treatment drugs. Donepezil (0.5mgkg-1) was used as a positive control. Results: 2K1C rats showed reduction in learning, memory, reversal learning, executive functioning, impairment in endothelial function, increase in mean artery blood pressure, brains’ oxidative stress, inflammation, calcium levels, and AchE-activity. Administration of nicergoline significantly attenuated the 2K1C induced impairments in the behavioral, endothelial, and biochemical parameters. Conclusion: 2K1C renovascular hypertension induced impairment in behavioral, endothelial, and biochemical parameters which were attenuated by the administration of nicergoline. Therefore, nicergoline may be studied further for the assessment of their full potential in hypertension induced VaD.
Cite this article:
B.M. Sharma, Bhupesh Sharma. Evaluation of involvement of adrenergic receptor modulator in hypertension induced experimental Vascular Dementia in Rats. Research Journal of Pharmacy and Technology. 2021; 14(12):6669-5. doi: 10.52711/0974-360X.2021.01152
B.M. Sharma, Bhupesh Sharma. Evaluation of involvement of adrenergic receptor modulator in hypertension induced experimental Vascular Dementia in Rats. Research Journal of Pharmacy and Technology. 2021; 14(12):6669-5. doi: 10.52711/0974-360X.2021.01152 Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-12-82
1. O’Brien JT, Thomas A. Vascular dementia. The Lancet 2015; 386(10004):1698–706.
2. Wang J, Zhang H, Tang X. Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment. Acta Pharmaceutica Sinica B 2009; 30:879–88.
3. Kumar ATK. An Insight into Assessment and Management of Dementia. International journal of advances in nursing management. 2014; 2(3): 180-182.
4. Faraco G, Iadecola C. Hypertension: A Harbinger of Stroke and Dementia. Hypertension, 2013; 62(5): 810–817.
5. Pires PW, Dams Ramos CM, Matin N, Dorrance AM. The effects of hypertension on the cerebral circulation. The American Journal of Physiology. Heart and Circulatory Physiology. 2013; 304 (12):H1598–H1614
6. Singh P, Gupta S, Sharma B. Melatonin receptor and KATP channel modulation in experimental vascular dementia. Physiology and Behavior. 2015; 142: 66-78.
7. Singh P, Gupta S, Sharma B. Antagonism of Endothelin (ETA and ETB) Receptors During Renovascular Hypertension-Induced Vascular Dementia Improves Cognition. Current Neurovascular Research. 2016; 13: 1-12
8. Soni S, Kumar P, Verma VS, Sharma M. Significance of Indian Medicinal Plants used for Treatment of Dementia. Asian journal of research in pharmaceutical sciences. 2014; 4(4) 202-205.
9. Saletu, B., Garg, A., and Shoeb, A. Safety of Nicergoline as an Agent for Management of Cognitive Function Disorders. BioMed Research International, 2014; 1–6.
10. Chandra P, Paul A. The Effects of Nicergoline and Other Vaso-Active Substances on Molecular Biological Processes in the Brain and Their Effects on the Learning Abilities of Rats. In: Heidrich H. (eds) Proof of Therapeutical Effectiveness of Nootropic and Vasoactive Drugs. Springer, Berlin, Heidelberg. 1986
11. Zang G, Fang L, Chen L,Wang C. Ameliorative effect of nicergoline on cognitive function through the PI3K/AKT signaling pathway in mouse models of Alzheimer’s disease. Molecular Medicine Reports. 2018; 7293-7300
12. Tanaka M, Yoshida T, Okamoto K, Hirai S. Antioxidant properties of nicergoline; inhibition of brain auto-oxidation and superoxide production of neutrophils in rats. Neuroscience Letters. 1998; 248(1): 68–72.
13. Giardino L, Gioliani A, Battaglia A. Neuroprotection and aging of the cholinergic system: A role for the ergoline derivative nicergoline (Sermion®). Neuroscience. 2000; 109(3):487-497
14. Jing L, Zhang JZ, Wang YL, Guo FY. Over-expression of extracellular signal-regulated kinase in vascular smooth muscle cell of hypertensive rats. Chinese Medical Sciences Journal. 2006; 21(1): 36-40.
15. Groó D, Pálosi É, Szporn L. Comparison of the effects of vinpocetine, vincamine, and nicergoline on the normal and hypoxia-damaged learning process in spontaneously hypertensive rats. Drug Development Research. 1988; 15(1), 75–85.
16. Singh P, Sharma B. Selective Serotonin-norepinephrine Re-uptake Inhibition Limits Renovascular- hypertension Induced Cognitive Impairment, Endothelial Dysfunction, and Oxidative Stress Injury. Current Neurovascular Research. 2016; 13.
17. Jain S, Sharma B. Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia. Physiology and Behavior. 2015; 152:182–93.
18. Sharma B, Singh N. Pitavastatin and 4′-hydroxy-3′-methoxyacetophenone (HMAP) reduce cognitive dysfunction in vascular dementia during experimental diabetes. Current Neurovascular Research. 2010; 7:180–91.
19. Sharma B, Singh N. Attenuation of vascular dementia by sodium butyrate in streptozotocin diabetic rats. Psychopharmacology (Berl). 2011a; 215:677–87.
20. Sharma B, Singh N. Behavioral and biochemical investigations to explore pharmacological potential of PPAR-gamma agonists in vascular dementia of diabetic rats. Pharmacology Biochemistry and Behavior. 2011b; 100:320–9.
21. Singh G, Sharma B, Jaggi AS, Singh N. Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats. Pharmacology Biochemistry and Behavior. 2014; 124:27-35.
22. Gupta S, Sharma B. Pharmacological benefits of agomelatine and vanillin in experimental model of Huntington's disease. Pharmacology Biochemistry and Behavior. 2014; 122:122–135.
23. Sharma B, Singh N. Experimental hypertension induced vascular dementia: pharmacological biochemical and behavioral recuperation by angiotensin receptor blocker and acetylcholinesterase inhibitor. Pharmacology Biochemistry and Behavior. 2012a; 102(1):101–8.
24. Sharma P, Kulkarni GT, Sharma B. Possible involvement of D2/D3 receptor activation in ischemic preconditioning mediated protection of the brain. Brain Research. 2020; 1748:147116.
25. De Simone G, Devereux RB, Camargo MJ, Wallerson DC, Laragh JH. Influence of sodium intake on in vivo left ventricular anatomy in experimental renovascular hypertension. The American Journal of Physiology. 1993; 264(part 2):H2103-H2110.
26. Corbier A, Lecaque D, Secchi J, Depouez B, Ramon G. Effect of 4 weeks of treatment with trandolapril on renal hypertension and cardiac and vascular hypertrophy in the rat. Journal of Cardiovascular Pharmacology and Therapeutics. 1994; 23(suppl 4):S26-S29.
27. Zhang, Y. H. (2016). Neuronal nitric oxide synthase in hypertension – an update. Clinical Hypertension, 22(1).
28. Al-Hatamleh MA, Al-Shajrawi OM, Khan S, Nadeem MI, Simbak NB, Latif ZA, Baig AA, Ariff TM. Effects of Oxidative Stress on Alzheimer's Disease, Haematological Perspective. Research Journal of Pharmacy and Technology. 2018; 11(9): 3881-3886.
29. Derouiche S, Cheradid T, Guessoum M. Heavy metals. Oxidative stress and Inflammation in Pathophysiology of Chronic Kidney disease - A Review. Asian journal of pharmacy and technology. 2020; 10(3):202-206.
30. Bhardwaj JS, Manandhar S, Chatterjee S, Hari G, Priya K, Raviteja S, Pai SR. Protective Effects of Gossypin in Colchicine-induced Cognitive Dysfunction and Oxidative Damage in Rats. Research journal of pharmacy and technology. 2020; 13(11):5189-5196.
31. Widder JD, Fraccarollo D, Galuppo P, Hansen JM, Jones DP, Ertl G, Bauersachs J. Attenuation of angiotensin II-induced vascular dysfunction and hypertension by overexpression of Thioredoxin 2. Hypertension. 2009; 54(2):338-44.
32. Doughan AK, Harrison DG, Dikalov SI. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circulation Research. 2008; 102(4):488-96.
33. Julius A, Renugadevi K, Hemavathy V. Effect of Oxidative Stress in Essential Hypertension. Research Journal of Pharmacy and Technology. 2014; 7(12): 1400-1403.
34. Yogesh N. Gholse, Manjusha P. Yeole, Shailju G. Gurunani. Inflammasomes: Types and Activation. Research journal of pharmacy and technology. 2014; 7(6): 695-703.
35. De Miguel , Rudemiller NP, Abais JM, Mattson DL. Inflammation and Hypertension: New Understandings and Potential Therapeutic Targets. Current Hypertension Reports. 2014; 17(1).
36. Raju MG, Srilakshmi S. Anti-Amnesic effect of methanolic extract of Tagetes erecta flower heads on Aluminium Induced Cognitive Impairment in Albino Mice. Research journal of pharmacognosy and phytochemistry. 2018; 10(4): 299-303.
37. Odegaard AO, Jacobs D R, Sanchez OA, Goff DC, Reine AP, Gross M D. Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes. Cardiovascular Diabetology. 2016; 15:51.
38. Huchet AM, Schmitt H. The effects of nicergoline on the heart rate in the normotensive or spontaneously hypertensive rat. Possible participation of central alpha-1 receptors. The Journal of Pharmacology and Pharmacotherapeutics. 1986;17(1):53-9.
39. Mizuno T, Kuno R, Nitta A, Nabeshima T. Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes. Brain Research. 2006; 1066:78-85.
40. Lagarde M, Guichardant M, Ghazi I, Dechavanne M. Nicergoline, an anti-aggregating agent which inhibits release of arachidonic acid from human platelet phospholipids. Prostaglandins. 1980; 19:551-7.
41. Iwata E, Miyazaki L, Asanuma M, Lida A, Ogawa N. Protective effects of nicergoline against hydrogen peroxide toxicity in rat neuronal cell line. Neuroscience Letters. 1998; 251(1):49-52
42. Sudha R, Sukumaran SK. Anti-Oxidants used for the Treatment of Alzheimer Disease. Research Journal of Pharmacy and Technology. 2020; 13(1): 475-480.
43. Kumar DR, Shankar MS, Reddy PP, Kumar RS, Sumalatha N. A Review on Alzheimer’s Disease. Research Journal of Pharmacology and Pharmacodynamics. 2014; 6(1): 59-63.