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

C. Hass; B. P. Panda; R. Khanam; A. K. Najmi; M. Akhtar

doi:10.1055/s-0035-1569448

Drug Research, Table of Contents

Drug Res (Stuttg) 2016; 66(06): 324-329
DOI: 10.1055/s-0035-1569448

Original Article

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

C. Hass

¹Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India

,

B. P. Panda

²Department of Biotechnology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India

,

R. Khanam

³Department of Pharmacology, Gulf Medical University, Ajman, UAE

,

A. K. Najmi

¹Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India

,

M. Akhtar

¹Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India

› Author Affiliations

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

Full Text

References

References
1 Rao BH. Global burden of Sudden Cardiac Death and insights from India. Indian heart J 2014; 66S1: S18-S23
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
18 Levi R, Smith NC. Histamine H(3)-receptors: a new frontier in myocardial ischemia. J Pharmacol Exp Therap 2000; 292: 825-830
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
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
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
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
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
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
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
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
27 Mishra HP, Fridovich I. The oxidation of phenylhydrazine: superoxide and mechanisms. Biochemistry 1976; 15: 681-687
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
29 Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82: 70-77
30 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
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
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
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
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
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
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
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
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
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
40 Pearce RM. Experimental myocarditis; a study of the histological changes following intravenous injections of adrenalin. The J Exp Med 1906; 8: 400-409
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
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
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
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
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
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
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