Abstract
We observed changes of intermedin (IMD) and its receptor system mRNA expressed with renal ischemia/reperfusion (I/R) injury in the rat and explored the protective effects of IMD pretreatment on renal injury. In comparison with sham group kidneys, I/R-injured rats had severe pathological changes; renal superoxide dismutase (SOD) was decreased (−34.8%) and tissue malondialdehyde (MDA) was increased (+34%; both p<0.01); renal IMD content and mRNA levels were decreased by 63.5% and 48.2%, respectively (both p<0.01); and CRLR, RAMP1, and RAMP3 mRNA levels were decreased by 39.5%, 11.2%, and 21.2%, respectively (all p<0.01). After pretreatment with IMD (1.0 and 5.0 nmol/kg) and ADM (5.0 nmol/kg), MDA content was lowered by 49.2%, 37.3%, and 36.9% respectively (all p<0.01) and SOD activity was increased by 37.2%, 22.1%, and 19.7%, respectively (all p<0.01). Thus, renal I/R injury in rat downregulated IMD and its receptor system and pretreatment with IMD attenuated I/R-induced renal functional and structural damage.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Roh J, Chang C L, Bhalla A, et al. Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes [J]. J Biol Chem, 2004, 279(8): 7264–7274.
Takei Y, Inoue K, Ogoshi M, et al. Identification of novel adrenomedullin in mammals: A potent cardiovascular and renal regulator [J]. FEBS Lett, 2004, 556(1–3): 53–58.
Ren Y S, Yang J H, Zhang J, et al. Intermedin 1–53 in central nervous system elevates arterial blood pressure in rats [J]. Peptides, 2006, 27: 74–79.
Pan C S, Yang J H, Cai D Y, et al. Cardiovascular effects of newly discovered peptide intermedin/adrenomedullin 2 [J]. Peptides, 2005, 26: 1640–1646.
Zhao Y, Bell D, Smith L R, et al. Differential expression of components of the cardiomyocyte adrenomedullin/intermedin receptor system following blood pressure reduction in nitric oxide deficient hypertension [J]. J of Phar and Expe Ther, 2006, 316: 1269–1281.
Kuwasako K, Cao Y N, Nagoshi Y, et al. Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins [J]. Mol Pharmacol, 2004, 5: 207–213.
Takei Y, Hyodo S, Katafuchi T, et al. Novel fish-derived adrenomedullin in mammals: structure and possible function [J]. Peptides, 2004, 25: 1643–1656.
Takahashi K, Kikuchi K, Maruyama Y, et al. Immunocytochemical localization of adrenomedullin 2/intermedin-like immunoreactivity in human hypothalamus, heart and kidney [J]. Peptides, 2006, 27(6): 1383–1389.
Charles C J, Rademaker M T, Richards A M. Hemodynamic, hormonal and renal actions of adrenomedullin-2 in normal conscious sheep [J]. Endocrinology, 2006, 147: 1871–1877.
Fujisawa Y, Nagai Y, Miyatake A, et al. Renal effects of a new member of adrenomedullin family, adrenomedullin2, in rats [J]. Eur J Pharmacol, 2004, 497(1): 75–80.
Fujisawa Y, Nagai Y, Miyatake A, et al. Roles of adrenomedullin-2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats [J]. Am J Physiol, 2006, 290: H1120–H1127.
Fujisawa Y, Nagai Y, Miyatake A, et al. Effects of adrenomedullin-2 on regional hemodynamics in conscious rats [J]. Eur J Pharmacol, 2007, 558: 128–132.
Yang J H, Jia Y X, Pan C S, et al. Effects of intermedin 1–53 on cardiac function and ischemia/reperfusion injury in isolated rat hearts [J]. Biochem Biophys Res Commun, 2005, 327: 713–719.
Jia Y X, Yang J H, Pan C S, et al. Intermedin 1–53 protects the heart against isoproterenol induced ischemic injury in rats [J]. Eur J Pharmacol, 2006, 549: 117–123.
Chen B, Shi H B, Zhang X J, et al. Protective effect of intermedin pretreating on ischemia reperfusion injury to the rat kidney [J]. Journal of Clinical Urology, 2008, 23(5): 385–388.
Adin C A, Croker B P, Agarwal A. Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney [J]. Am J Physiol Renal Physiol, 2005, 288(4): 778–784.
Hauet T, Mothes D, Goujon J M, et al. Protective effect of polyethylene glycol against prolonged cold ischemia and reperfusion injury: study in the isolated perfused rat kidney [J]. J Pharmacol Exp Ther, 2001, 297(3): 946–952.
Aragno M, Cutrin J C, Mastrocola R, et al. Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: attenuation by dehydroepiandrosterone [J]. Kidney Int, 2003, 64: 836–843.
Yang J H, Pan C S, Jia Y X, et al. Intermedin 1–53 activates L-arginine/nitric oxide synthase/nitric oxide pathway in rat aortas [J]. Biochemical and Biophysical Research Communications, 2006, 341: 567–572.
Guz G, Demirogullari B, Ulusu N N, et al. Stobadine protects rat kidney against ischaemia/reperfusion injury [J]. Clin Exp Pharmacol Physiol, 2007, 34(3): 210–216.
Gong Y S, Fan X F, Wu X M, et al. Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle of rats with chronic hypoxic pulmonary hypertension [J]. Acta Physiologia Sinica, 2007, 59(2): 210–214.
McDermott B J, Zhao Y Y, McCoy F G P, et al. Upregulation of intermedin and reduced neutral endopeptidase expression in hypertensive cardiac hypertrophy [J]. J Mol Cell Cardiol, 2007, 42: 5134.
Bell D, Zhao Y, McCoy F P, et al. Differential effects of an anti-oxidant intervention on cardiomyocyte expression of adrenomedullin and intermedin and their receptor components in chronic nitric oxide deficiency [J]. Cell Physiol Biochem, 2007, 20: 269–282.
Hirose T, Totsune K, Mori N, et al. Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure [J]. Eur J Heart Fail, 2008, 10(9): 840–849.
Nishikimi T, Yoshihara F, Kanazawa A, et al. Role of increased circulation and renal adrenomedullin in rats with malignant hypertension [J]. Am J Physiol Regul Integr Physiol, 2001, 281(6): R2079–2087.
Nishikimi T. Adrenomedullin in the kidney renal physiological and pathophysiological [J]. Current Medicinal Chemistry, 2007, 14(15): 1689–1699.
Nagae T, Mukoyama M, Sugawara A, et al. Rat receptor-activity-modifying proteins(RAMPs) for adrenomedullin/CGRP receptor: cloning and upregulation in obstructive nephropathy [J]. Biochem Biophys Res Commun, 2000, 270(1): 89–93.
Nishikimi T. Adrenomedullin in the kidney renal physiological and pathophysiological [J]. Current Medicinal Chemistry, 2007, 14(15): 1689–1699.
Author information
Authors and Affiliations
Corresponding author
Additional information
Foundation item: Supported by the Hubei Provincial Department of Education Science Foundation (B200524007) and the Xiangfan Central Hospital Science Foundation (XFCH200601)
Biography: YUAN Jie, male, Master, Associate professor, research direction: pathology and physiology of peptides.
These authors contributed equally to this work.
Rights and permissions
About this article
Cite this article
Yuan, J., Chen, B., Ren, Y. et al. Protective effects of I/A 2 on ischemia/reperfusion injury in the isolated rat kidney. Wuhan Univ. J. Nat. Sci. 18, 178–184 (2013). https://doi.org/10.1007/s11859-013-0911-2
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11859-013-0911-2