Download PDF
Drug Res (Stuttg) 2016; 66(06): 324-329
DOI: 10.1055/s-0035-1569448
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Histamine H3 Receptor Agonist Imetit Attenuated Isoproterenol Induced Renin Angiotensin System and Sympathetic Nervous System Overactivity in Myocardial Infarction of Rats

C. Hass
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
,
B. P. Panda
2   Department of Biotechnology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
,
R. Khanam
3   Department of Pharmacology, Gulf Medical University, Ajman, UAE
,
A. K. Najmi
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
,
M. Akhtar
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
› Author Affiliations
Further Information

Publication History

received 29 January 2016

accepted 19 February 2016

Publication Date:
24 March 2016 (online)

Also available at
    Permissions and Reprints

Abstract

Background: Myocardial infarction is an alarming health issue, needs great attention. The present study investigated the role of histamine-H3 receptor (H3R) agonist imetit in relationship to sympathetic and renin angiotensin system in Wistar rats.

Materials and Methods: Subcutaneous injection of isoproterenol (85 mg/kg) on last 2 consecutive days in per se group and 7 days treatment of different groups at 24 h interval induced myocardial infarction in Wistar rats. H3R agonist imetit (10 mg/kg), H3R antagonist thioperamide (5 mg/kg), losartan (10 mg/kg) were administered orally to evaluate imetit’s cardioprotective potential effect by measuring plasma cardiac antioxidant markers, angiotensin II, norepinephrine levels and histopathological analysis.

Results: Isoproterenol significantly elevated the angiotensin II and norepinephrine levels in rat plasma. This study revealed that pre-treatment with imetit similar to losartan attenuated norepinephrine and angiotensin II levels whereas thioperamide showed its antagonistic effect by diminishing imetit’s effects. Furthermore, its protective effect was confirmed by restoration of cardiac antioxidant markers and histopathological improvement of myocardium integrity.

Conclusion: This study confirm imetit’s cardioprotective potential and also reveals renin angiotensin system, sympathetic system and H3R correlation in isoproterenol induced toxicity in rats. However, molecular studies must be warranted to prove the role of H3R in myocardial infarction.

Key words

imetit - isoproterenol - thioperamide - renin angiotensin system - norepinephrine
 

  • References

  • 1 Rao BH. Global burden of Sudden Cardiac Death and insights from India. Indian heart J 2014; 66S1: S18-S23
    PubMedGoogle Scholar
  • 2 Alwan A, Maclean DR, Riley LM et al. Monitoring and surveillance of chronic non-communicable diseases: progress and capacity in high-burden countries. Lancet 2010; 376: 1861-1868
    CrossrefPubMedGoogle Scholar
  • 3 Kameda K, Matsunaga T, Abe N et al. Correlation of oxidative stress with activity of matrix metalloproteinase in patients with coronary artery disease. Possible role for left ventricular remodelling. Eur Heart J 2003; 24: 2180-2185
    CrossrefPubMedGoogle Scholar
  • 4 Francis GS. The relationship of the sympathetic nervous system and the renin-angiotensin system in congestive heart failure. Am Heart J 1989; 118: 642-648
    CrossrefPubMedGoogle Scholar
  • 5 Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Phys 2007; 292: 82-97
    PubMedGoogle Scholar
  • 6 Xi XP, Graf K, Goetze S et al. Central role of the MAPK pathway in Ang II-mediated DNA synthesis and migration in rat vascular smooth muscle cells. Arteriosclerosis Thrombosis Vascular Biology 1999; 19: 73-82
    CrossrefPubMedGoogle Scholar
  • 7 Toklu HZ, Kwon OS, Sakarya Y et al. The effects of enalapril and losartan on mechanical ventilation-induced sympathoadrenal activation and oxidative stress in rats. J Surg Res 2014; 188: 510-516
    CrossrefPubMedGoogle Scholar
  • 8 Bos R, Mougenot N, Findji L et al. Inhibition of catecholamine-induced cardiac fibrosis by an aldosterone antagonist. J Cardiovas Pharmacol 2005; 45: 8-13
    CrossrefPubMedGoogle Scholar
  • 9 Sethi R, Shao Q, Ren B et al. Changes in beta-adrenoceptors in heart failure due to myocardial infarction are attenuated by blockade of renin-angiotensin system. Mol Cell Biochem 2004; 263: 11-20
    CrossrefPubMedGoogle Scholar
  • 10 Igawa A, Nozawa T, Yoshida N et al. Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and beta-adrenergic desensitization in heart failure after myocardial infarction in rats. Jap Heart J 2002; 43: 675-688
    CrossrefPubMedGoogle Scholar
  • 11 Abdulla MH, Sattar MA, Abdullah NA et al. Inhibition of Ang II and renal sympathetic nerve influence dopamine-and isoprenaline-induced renal haemodynamic changes in normal Wistar-Kyoto and spontaneously hypertensive rats. Auton Auto Pharmacol 2008; 28: 95-101
    PubMedGoogle Scholar
  • 12 K-Laflamme A, Oster L, Cardinal R et al. Effects of renin-angiotensin blockade on sympathetic reactivity and beta-adrenergic pathway in the spontaneously hypertensive rat. Hypertension 1997; 30: 278-287
    CrossrefPubMedGoogle Scholar
  • 13 Akers WS, Cross A, Speth R et al. Renin-angiotensin system and sympathetic nervous system in cardiac pressure-overload hypertrophy. Am J Physiol Heart Circul Physiol 2000; 279: H2797-H2806
    PubMedGoogle Scholar
  • 14 Imamura M, Lander HM, Levi R. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha2-adrenoceptors. Cir Res 1996; 78: 475-481
    CrossrefPubMedGoogle Scholar
  • 15 Imamura M, Seyedi N, Lander HM et al. Functional identification of histamine H3-receptors in the human heart. Cir Res 1995; 77: 206-210
    CrossrefPubMedGoogle Scholar
  • 16 Imamura M, Seyedi N, Lander HM et al. Histamine H3-receptor-mediated inhibition of calcitonin gene-related peptide release from cardiac C fibers. A regulatory negative-feedback loop. Cir Res 1996; 78: 863-869
    CrossrefPubMedGoogle Scholar
  • 17 Levi R, Seyedi N, Schaefer U et al. Histamine H3-receptor signaling in cardiac sympathetic nerves: Identification of a novel MAPK-PLA2-COX-PGE2-EP3R pathway. Biochem Pharmacol 2007; 73: 1146-1156
    CrossrefPubMedGoogle Scholar
  • 18 Levi R, Smith NC. Histamine H(3)-receptors: a new frontier in myocardial ischemia. J Pharmacol Exp Therap 2000; 292: 825-830
    PubMedGoogle Scholar
  • 19 Mazenot C, Ribuot C, Durand A et al. In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-alpha-methyl-histamine and its prodrug BP 2.94 in the dog. Br J Pharmacol 1999; 126: 264-268
    CrossrefPubMedGoogle Scholar
  • 20 Hatta E, Yasuda K, Levi R. Activation of histamine H3 receptors inhibits carrier-mediated norepinephrine release in a human model of protracted myocardial ischemia. J Pharmacol Exp Ther 1997; 283: 494-500
    PubMedGoogle Scholar
  • 21 Seyedi N, Mackins CJ, Machida T et al. Histamine H3-receptor-induced attenuation of norepinephrine exocytosis: a decreased protein kinase a activity mediates a reduction in intracellular calcium. J Pharmacol Exp Ther 2005; 312: 272-280
    PubMedGoogle Scholar
  • 22 Silver RB, Poonwasi KS, Seyedi N et al. Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings. Proc Nat Acad Sci United States America 2002; 99: 501-506
    PubMedGoogle Scholar
  • 23 Hashikawa-Hobara N, Chan NY, Levi R. Histamine 3 receptor activation reduces the expression of neuronal angiotensin II type 1 receptors in the heart. J Pharmacol Exp Ther 2012; 340: 185-191
    CrossrefPubMedGoogle Scholar
  • 24 Yadav CH, Akhtar M, Khanam R. Isoproterenol toxicity induced ECG alterations in wistar rats: role of histamine H3 receptor agonist imetit. Int J Pharm Pharm Sci 2014; 6: 654-658
    PubMedGoogle Scholar
  • 25 Luo B, Zhang S, Shoucun M et al. Effects of cold air on cardiovascular disease risk factors in rat. Int J Environ Res Pub Health 2012; 9: 2312-2325
    CrossrefPubMedGoogle Scholar
  • 26 Skurk T, Lee YM, Hauner H. Angiotensin II and its metabolites stimulates PAI-1 protein release from human adipocytes in primary culture. Hypertension 2001; 37: 1336-1340
    CrossrefPubMedGoogle Scholar
  • 27 Mishra HP, Fridovich I. The oxidation of phenylhydrazine: superoxide and mechanisms. Biochemistry 1976; 15: 681-687
    CrossrefPubMedGoogle Scholar
  • 28 Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968; 25: 192-205
    CrossrefPubMedGoogle Scholar
  • 29 Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82: 70-77
    CrossrefPubMedGoogle Scholar
  • 30 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
    CrossrefPubMedGoogle Scholar
  • 31 Goyal S, Arora S, Mittal R et al. Myocardial salvaging effect of telmisartan in experimental model of myocardial infarction. Eur J Pharmacol 2009; 619: 75-84
    CrossrefPubMedGoogle Scholar
  • 32 Rona G, Zsoter T, Chappel C et al. Myocardial lesions, circulatory and electrocardiographic changes produced by isoproterenol in the dog. Revue canadienne de biologie/editee par l'Universite de Montreal 1959; 18: 83-94
    PubMedGoogle Scholar
  • 33 De Biase L, Pignatelli P, Lenti L et al. Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O2- production. Thromb Haemost 2003; 90: 317-325
    PubMedGoogle Scholar
  • 34 Rajadurai M, Prince PS. Preventive effect of naringin on isoproterenol-induced cardiotoxicity in Wistar rats: an in vivo and in vitro study. Toxicol 2007; 232: 216-225
    CrossrefPubMedGoogle Scholar
  • 35 Chang PC, Kriek E, van der Krogt JA et al. Stimulation of norepinephrine release by peripheral presynaptic beta-adrenoceptors. Clin Exper Hyperten Part A, Theory and practice 1989; 11: 311-321
    PubMedGoogle Scholar
  • 36 Soraya H, Khorrami A, Garjani A et al. Acute treatment with metformin improves cardiac function following isoproterenol induced myocardial infarction in rats. Pharmacol Rep 2012; 64: 1476-1484
    CrossrefPubMedGoogle Scholar
  • 37 Yates JC, Dhalla NS. Induction of necrosis and failure in the isolated perfused rat heart with oxidized isoproterenol. J Mol Cell Card 1975; 7: 807-816
    CrossrefPubMedGoogle Scholar
  • 38 Grimm D, Elsner D, Schunkert H et al. Development of heart failure following isoproterenol administration in the rat: role of the renin-angiotensin system. Card Res 1998; 37: 91-100
    CrossrefPubMedGoogle Scholar
  • 39 Leenen FH, White R, Yuan B. Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system. Am J Physiol Heart Cir Phys 2001; 281: H2410-H2416
    PubMedGoogle Scholar
  • 40 Pearce RM. Experimental myocarditis; a study of the histological changes following intravenous injections of adrenalin. The J Exp Med 1906; 8: 400-409
    PubMedGoogle Scholar
  • 41 Kahan T, Dahlof C, Hjemdahl P. Facilitation of nerve stimulation evoked noradrenaline overflow by isoprenaline but not by circulating adrenaline in the dog in vivo. Life Sci 1987; 40: 1811-1818
    CrossrefPubMedGoogle Scholar
  • 42 Barki-Harrington L, Luttrell LM, Rockman HA. Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist: a functional role for receptor-receptor interaction in vivo. Circ 2003; 108: 1611-1618
    CrossrefPubMedGoogle Scholar
  • 43 Neri M, Cerretani D, Fiaschi AI et al. Correlation between cardiac oxidative stress and myocardial pathology due to acute and chronic norepinephrine administration in rats. J Cell Mol Med 2007; 11: 156-170
    CrossrefPubMedGoogle Scholar
  • 44 Bertagnolli M, Schenkel PC, Campos C et al. Exercise training reduces sympathetic modulation on cardiovascular system and cardiac oxidative stress in spontaneously hypertensive rats. Am J Hypertension 2008; 21: 1188-1193
    CrossrefPubMedGoogle Scholar
  • 45 Kim HK, Park WS, Warda M et al. Beta adrenergic overstimulation impaired vascular contractility via actin-cytoskeleton disorganization in rabbit cerebral artery. PLoS One 2012; 7: 43884
    CrossrefPubMedGoogle Scholar
  • 46 Rathore N, John S, Kale M et al. Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res 1998; 38: 297-303
    CrossrefPubMedGoogle Scholar
  • 47 Ithayarasi AP, Devi CS. Effect of alpha-tocopherol on lipid peroxidation in isoproterenol induced myocardial infarction in rats. Indian J Physiol Pharmacol 1997; 41: 369-376
    PubMedGoogle Scholar