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Central European Journal of Medicine

, Volume 6, Issue 3, pp 331–340 | Cite as

Effects of angiotensin II receptor antagonists on anxiety and some oxidative stress markers in rat

  • Alin Ciobica
  • Veronica Bild
  • Lucian Hritcu
  • Manuela Padurariu
  • Walther Bild
Research Article

Abstract

In addition to its known classical roles, the renin angiotensin system (RAS) has more subtle functions which include the regulation of emotional responses. Previous studies regarding the anxiety related behavior of RAS have showed controversial results. There is also evidence that oxidative stress accompanies angiotensin II infusion, but the role of AT1/AT2 specific receptors is not clear. The aim of this study was to evaluate the effects of central angiotensin II receptor blockers on anxiety state and oxidative stress. Behavioral testing included elevated plus maze, while oxidative stress status was measured though the extent of a lipid peroxidation product (malondialdehyde-MDA) and the specific activity of some defense antioxidant enzymes (superoxide dismutase-SOD and glutathione peroxidase-GPx). The rats treated with angiotensin II spent significantly less time in the open-arms of elevated-plus-maze, while the administration of losartan resulted in a significant increase of this time. We observed a significant increase of MDA concentration in the angiotensin II group and a decrease of MDA levels in both losartan and PD-123177 groups. In addition, a significant correlation was seen between the time spent in the open arms and oxidative stress markers. These findings could lead to important therapeutic aspects regarding the use of angiotensin II receptor blockers in anxiety-related disorders.

Keywords

Angiotensin II Losartan PD-123177 Anxiety Oxidative stress 

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References

  1. [1]
    Von Bohlen und Halbach O, Albrecht D. The CNS rennin angiotensin system. Cell Tissue Res. 2006;326: 599–616CrossRefGoogle Scholar
  2. [2]
    Haulica I, Bild W, Serban DN. Angiotensin peptides and their pleiotropic actions. J Renin Angiotensin Aldosterone Syst. 2005;6: 121–131PubMedCrossRefGoogle Scholar
  3. [3]
    Ciobica A, Bild W, Hritcu L, Haulica I. Brain reninangiotensin system in cognitive function: preclinical findings and implications for prevention and treatment of dementia. Acta Neurol Belg. 2009;109: 171–180PubMedGoogle Scholar
  4. [4]
    Gard PR. Angiotensin as a target for the treatment of Alzheimer’s disease, anxiety and depression. Expert Opin Ther Targets. 2004;8: 7–14PubMedCrossRefGoogle Scholar
  5. [5]
    Braszko JJ, Kułakowska A, Winnicka MM. Effects of angiotensin II and its receptor antagonists on motor activity and anxiety in rats. J Physiol Pharmacol. 2003;54: 271–281PubMedGoogle Scholar
  6. [6]
    Llorens-Cortes C, Mendelsohn FA. Organisation and functional role of the brain angiotensin system. J Renin Angiotensin Aldosterone Syst. 2002;3suppl 1:39–48CrossRefGoogle Scholar
  7. [7]
    de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000;52: 415–472PubMedGoogle Scholar
  8. [8]
    Hritcu L, Bild W, Ciobica A, Artenie V, Haulica I. Behavioral changes induced by angiotensin AT1 receptors blockade in the rat brain. Eur. Psychiatry. 2009;24suppl 1:S859CrossRefGoogle Scholar
  9. [9]
    Barnes NM, Costall B, Kelly ME, Murphy DA, Naylor RJ. Anxiolytic-like action of DuP753, a non-peptide angiotensin II receptor antagonist. Neuroreport. 1990;1: 20–21PubMedCrossRefGoogle Scholar
  10. [10]
    Kaiser FC, Palmer GC, Wallace AV, Carr RD, Fraser-Rae L, Hallam C. Antianxiety properties of the angiotensin II antagonist, DUP 753, in the rat using the elevated plus-maze. Neuroreport. 1992;3: 922–924PubMedCrossRefGoogle Scholar
  11. [11]
    Cambursano PT, Haigh SJ, Keightley J, Sutcliffe MA, Gard PR. Positive effects of losartan in laboratory tests indicative of anxiolytic-like activity and the importance of animal strain. J. Pharm. Pharmacol. 1997;49suppl. 4:64Google Scholar
  12. [12]
    Srinivasan J, Suresh B, Ramanathan M. Differential anxiolytic effect of enalapril and losartan in normotensive and renal hypertensive rats. Physiol Behav. 2003;78: 585–591PubMedCrossRefGoogle Scholar
  13. [13]
    Kulakowska A, Karwowska W, Wisniewski K, Braszko JJ. Losartan influences behavioural effects of angiotensin II in rats. Pharmacol Res 1996;34: 109–115PubMedCrossRefGoogle Scholar
  14. [14]
    Shepherd J, Bill DJ, Dourish CT, Grewal SS, McLenachan A, Stanhope KJ. Effects of the selective angiotensin II receptor antagonists losartan and PD-123177 in animal models of anxiety and memory. Psychopharmacology (Berl). 1996;126: 206–218CrossRefGoogle Scholar
  15. [15]
    Okuyama S, Sakagawa T, Inagami T. Role of the angiotensin II type-2 receptor in the mouse central nervous system. Jpn J Pharmacol. 1999;81: 259–263PubMedCrossRefGoogle Scholar
  16. [16]
    Chabrashvili T, Kitiyakara C, Blau J, Karber A, Aslam S. Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression. Am J Physiol Regul Integr Comp Physiol. 2003;285: R117–R124PubMedGoogle Scholar
  17. [17]
    Wang D, Chabrashvili T, Borrego L, Aslam S, Umans JG. Angiotensin II infusion alters vascular function in mouse resistance vessels: roles of O and endothelium. J Vasc Res. 2006;43: 109–119PubMedCrossRefGoogle Scholar
  18. [18]
    Laursen JB, Rajagopalan B, Galis Z, Tarpey M, Freeman BA, Harrison DG. Role of superoxide in angiotensin II induced but not catecholamine-induced hypertension. Circulation. 1997;95: 588–593PubMedGoogle Scholar
  19. [19]
    Yao EH, Fukuda N, Matsumoto T, Kobayashi N, Katakawa M, Yamamoto C et al. Losartan improves the impaired function of endothelial progenitor cells in hypertension via an antioxidant effect. Hypertens Res. 2007;30: 1119–1128PubMedCrossRefGoogle Scholar
  20. [20]
    Antelava NA, Gongadze NV, Gogolauri MI. Comparative characteristic of angiotensin-converting enzyme inhibitor-captopril and the angiotensin II receptor blokers—losartan action on the oxidative metabolism in experimental hyperlipidemia in rabbits. Georgian Med News. 2007;150: 57–60PubMedGoogle Scholar
  21. [21]
    Yanagitani Y, Rakugi H, Okamura A, Moriguchi K, Takiuchi S, Ohishi M et al. Angiotensin II type 1 receptor-mediated peroxide production in human macrophages. Hypertension. 1999;33: 335–339PubMedGoogle Scholar
  22. [22]
    Bouayed, J., Rammal, H., Younos, C., Soulimani, R., 2007b. Positive correlation between peripheral blood granulocyte oxidative status and level of anxiety in mice. Eur. J. Phar macol. 564, 146–149CrossRefGoogle Scholar
  23. [23]
    Karelson E, Bogdanovic N, Garlind A, Winblad B, Zilmer K et al. The cerebrocortical areas in normal brain aging and in Alzheimer’s disease: noticeable differences in the lipid peroxidation level and in antioxidant defense. Neurochem Res. 2001;26: 353–361PubMedCrossRefGoogle Scholar
  24. [24]
    Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. San Diego: Academic Press Elsevier; 2006Google Scholar
  25. [25]
    Ciobica A, Hritcu L, Padurariu M, Dobrin R, Bild V. Effects of serotonin depletion on behavior and neuronal oxidative stress status in rat: relevance for anxiety and affective disorders. Adv Med Sci. 2010;55: 289–296PubMedCrossRefGoogle Scholar
  26. [26]
    Ciobica A, Hritcu L, Artenie V, Stoica B, Bild V. Effects of 6-OHDA infusion into the hypothalamic paraventricular nucleus in mediating stress-induced behavioural responses and oxidative damage in rats. Acta Endocrinol. 2009;5: 425–436Google Scholar
  27. [27]
    Hritcu L, Ciobica A, Gorgan L. Nicotine-induced memory impairment by increasing brain oxidative stress. Cent. Eur. J. Biol. 2009;4: 335–342CrossRefGoogle Scholar
  28. [28]
    Gurzu C, Artenie V, Hritcu L, Ciobica A. Prenatal testosterone improves the spatial learning and memory by protein synthesis in different lobes of the brain in the male and female rat. Cent Eur J Biol. 2008;3: 39–47CrossRefGoogle Scholar
  29. [29]
    Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A et al. Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature. 1995;377: 748–750PubMedCrossRefGoogle Scholar
  30. [30]
    Okuyama S, Sakagawa T, Chaki S, Imagawa Y, Ichiki T, Inagami T. Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor. Brain Res. 1999;821: 150–159PubMedCrossRefGoogle Scholar
  31. [31]
    Gard PR, Haigh SJ, Cambursano PT, Warrington CA. Strain differences in the anxiolytic effects of losartan in the mouse. Pharmacol Biochem Behav. 2001;69: 35–40PubMedCrossRefGoogle Scholar
  32. [32]
    Georgiev V, Getova D, Opitz M. Mechanisms of the angiotensin II effects on the exploratory behavior of rats in open field. I. Interaction of angiotensin II with saralasin and catecholaminergic drugs. Methods Find Exp Clin Pharmacol. 1987;9: 297–301PubMedGoogle Scholar
  33. [33]
    Cresswell AG, Gard PR: Behavioural evidence of a paradoxical anxiogenic effect of an angiotensin II (AT1) receptor antagonist. J. Pharm. Pharmacol. 1998;50suppl 1:215Google Scholar
  34. [34]
    Peng JF, Phillips MI. Opposite regulation of brain angiotensin type 1 and type 2 receptors in coldinduced hypertension. Regul Peptides. 2001;97: 91–102CrossRefGoogle Scholar
  35. [35]
    Gelband CH, Zhu M, Lu D, Reagan LP, Fluharty SJ, Posner P et al. Functional interactions between neuronal AT1 and AT2 receptors. Endocrinology. 1997;138: 2195–2198PubMedCrossRefGoogle Scholar
  36. [36]
    Braszko JJ. AT(2) but not AT(1) receptor antagonism abolishes angiotensin II increase of the acquisition of conditioned avoidance responses in rats. Behav Brain Res. 2002;131: 79–86PubMedCrossRefGoogle Scholar
  37. [37]
    Bild W, Hritcu L, Ciobica A, Artenie V, Haulica I. Comparative effects of captopril, losartan and PD-123319 on the memory processes in rats. Eur. Psychiatry. 2009;24suppl 1:S860CrossRefGoogle Scholar
  38. [38]
    Bonini JS, Bevilaqua LR, Zinn CG, Kerr DS, Medina JH. et al. Angiotensin II disrupts inhibitory avoidance memory retrieval. Horm Behav. 2006;50: 308–313PubMedCrossRefGoogle Scholar
  39. [39]
    Kerr DS, Bevilaqua LR, Bonini JS, Rossato JI, Kohler CA, Medina JH. et al. Angiotensin II blocks memory consolidation through an AT2 receptor dependent mechanism. Psychopharmacology (Berl). 2005;179: 529–535CrossRefGoogle Scholar
  40. [40]
    Ciobica, W. Bild, I. Haulica, L. Hritcu, O. Arcan. Effects of angiotensin II, its receptor antagonists and captopril on cognitive functions and oxidative stress in rats. J. Neurol. 2009;256suppl 2:194Google Scholar
  41. [41]
    Ciobica A. Bild W. Hritcu L. Artenie V. Haulica I. The importance of oxidative stress in angiotensin II-mediated effects on cognitive functions. Neuropeptides. 2009;43: 420–421Google Scholar
  42. [42]
    Basso N, Cini R, Pietrelli A, Ferder L, Terragno NA. Protective effect of long-term angiotensin II inhibition. Am J Physiol Heart Circ Physiol. 2007;293: 1351–1358CrossRefGoogle Scholar
  43. [43]
    Holownia A, Braszko JJ. The effect of angiotensin II and IV on ERK1/2 and CREB signalling in cultured rat astroglial cells. Naunyn Schmiedebergs Arch Pharmacol. 2007;376: 157–163PubMedCrossRefGoogle Scholar
  44. [44]
    Padurariu M, Ciobica A, Hritcu L, Stoica B, Bild W., Stefanescu C. Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer’s disease. Neurosci Lett. 2010;469: 6–10PubMedCrossRefGoogle Scholar
  45. [45]
    Padurariu M, Ciobica A, Dobrin I, Stefanescu C. Evaluation of antioxidant enzymes activities and lipid peroxidation in schizophrenic patients treated with typical and atypical antipsychotics. Neurosci Lett. 2010;479: 317–320PubMedCrossRefGoogle Scholar
  46. [46]
    Hritcu L, Ciobica A, Artenie V. Effects of right-unilateral 6-hydroxydopamine infusion-induced memory impairment and oxidative stress: Relevance for Parkinson’s disease. Cent Eur J Biol. 2008;3: 250–257CrossRefGoogle Scholar
  47. [47]
    Berry A, Capone F, Giorgio M, Pelicci PG, de Kloet ER. Deletion of the life span determinant p66Shc prevents age-dependent increases in emotionality and pain sensitivity in mice. Exp Gerontol. 2007;42: 37–45PubMedCrossRefGoogle Scholar
  48. [48]
    Basso N, Altamirano S, Terragno NA, Ferder L, Inserra F. et al. Inhibition of the renin-angiotensin system improves spatial working memory in the senile normal rat. J Hypertens. 2002;20 suppl. 4:S134Google Scholar
  49. [49]
    Schupp N, Schmid U, Rutkowski P, Lakner U, Kanase N, Heidland A, Stopper H. Angiotensin II-induced genomic damage in renal cells can be prevented by angiotensin II type 1 receptor blockage or radical scavenging. Am J Physiol Renal Physiol. 2007 May;292(5):F1427–F1434PubMedCrossRefGoogle Scholar
  50. [50]
    Machado-Vieira R, Salvadore G, DiazGranados N, Ibrahim L, Latov D, Wheeler-Castillo C, Baumann J, Henter ID, Zarate CA Jr. New therapeutic targets for mood disorders. ScientificWorldJournal. 2010 Apr 13;10:713–726Google Scholar
  51. [51]
    Behl A, Swami G, Sircar SS, Bhatia MS, Banerjee BD. Relationship of possible stress-related biochemical markers to oxidative/antioxidative status in obsessive-compulsive disorder. Neuropsychobiology. 2010;61(4):210–214PubMedCrossRefGoogle Scholar
  52. [52]
    Matsushita M, Kumano-Go T, Suganuma N, Adachi H, Yamamura S, Morishima H, Shigedo Y, Mikami A, Takeda M, Sugita Y. Anxiety, neuroticism and oxidative stress: cross-sectional study in nonsmoking college students. Psychiatry Clin Neurosci. 2010 Aug;64(4):435–441PubMedCrossRefGoogle Scholar
  53. [53]
    Salim S, Sarraj N, Taneja M, Saha K, Tejada-Simon MV, Chugh G. Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats. Behav Brain Res. 2010 Apr 2;208(2):545–552CrossRefGoogle Scholar
  54. [54]
    Gingrich JA. Oxidative stress is the new stress. Nat Med. 2005;11(12):1281–1282PubMedCrossRefGoogle Scholar
  55. [55]
    Bouayed J, Rammal H, Soulimani R. Oxidative stress and anxiety: Relationship and cellular pathways. Oxid Med Cell Longev. 2009;2(2):63–67PubMedCrossRefGoogle Scholar
  56. [56]
    Rammal H, Bouayed J, Younos C, Soulimani R. Evidence that oxidative stress is linked to anxiety-related behaviour in mice. Brain Behav Immun. 2008;22(8):1156–1159PubMedCrossRefGoogle Scholar

Copyright information

© © Versita Warsaw and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Alin Ciobica
    • 1
  • Veronica Bild
    • 2
    • 3
  • Lucian Hritcu
    • 1
  • Manuela Padurariu
    • 2
  • Walther Bild
    • 2
    • 3
  1. 1.Department of BiologyAlexandru Ioan Cuza University UniversityIasiRomania
  2. 2.GR. T. Popa University of Medicine and PharmacyIasiRomania
  3. 3.Laboratory for Experimental and Applied PhysiologyRomanian AcademyIasiRomania

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