Effect of apelin on the cardiac hemodynamics in hypertensive rats with heart failure

Pang,Hui; Han,Bing; Yu,Tao; Zong,Zhenkun

doi:10.3892/ijmm.2014.1829

Effect of apelin on the cardiac hemodynamics in hypertensive rats with heart failure

Authors:
- Hui Pang
- Bing Han
- Tao Yu
- Zhenkun Zong
View Affiliations

Affiliations: Department of Cardiovascular Medicine, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, P.R. China, Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China
Published online on: July 2, 2014 https://doi.org/10.3892/ijmm.2014.1829
Pages: 756-764
Copyright: © Pang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

It is known that apelin has definite protective effects on various cardiovascular diseases; however, the mechanism through which hypertension with heart failure (H-HF) is affected by pyroglutamylated apelin-13 (Pyr-AP13) remain unclear. Thus, in the present study, we investigated the effects of apelin on the cardiac hemodynamics in rats with hypertension and heart failure. In our study, cardiac function, dimensions and histological determination of the fibrosis of rats with two-kidney, one-clip induced hypertension and sham-operated rats were assessed using an echocardiography system and Masson's trichrome. The infusion of either 5% glucose injection (GS) alone or 5% GS containing Pyr-AP13 as a dose, time-matched design on the cardiac hemodynamics in H-HF rats and sham-operated rats was recorded. For the determination of the effects of potential related proteins on cardiac hemodynamics in the H-HF rats, the animals were divided into 5 groups: i) the sham-operated group (n=8); ii) H-HF (n=8); iii) H-HF with infusion of 0.1 µg dose of Pyr-AP13 (n=8) or 5% glucose (GS) (n=8); iv) H-HF with infusion of 1 µg dose of Pyr-AP13 (n=8) or 5% GS (n=8); and v) H-HF with infusion of 10 µg dose of Pyr-AP13 (n=8) or 5% GS (n=8). The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) was determined by ELISA. The expression of membrane and cytosolic proteins was evaluated by western blot analysis. Significant cardiac and perivascular fibrosis was observed in the H-HF rats. Following the infusion of Pyr-AP13, the systolic and diastolic function was significantly improved in the cardiac hemodynamic parameters in the H-HF rats treated with Pyr-AP13. The apelin receptor (APJ), which was activated by the exogenous infusion of Pyr-AP13, was partially recycled from the cytoplasm back to the plasma membrane; however, membrane APJ was eventually downregulated in the H-HF rats treated with Pyr-AP13 compared with the sham-operated group rats. Our findings suggested that a complex was formed after Pyr-AP13 combined with cellular membrane APJ receptor. However, the endogenous downregulation of the APJ receptor results in benefits from the exogenous administration of apelin.

View Figures

View References

1	Tatemoto K, Hosoya M, Habata Y, et al: Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 251:471–476. 1998. View Article : Google Scholar : PubMed/NCBI
2	Maguire JJ, Kleinz MJ, Pitkin SL, et al: [Pyr¹] apelin-13 identified as the predominant apelin isoform in the human heart: vasoactive mechanisms and inotropic action in disease. Hypertension. 54:598–604. 2009.
3	Chun HJ, Ali ZA, Kojima Y, et al: Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. J Clin Invest. 118:3343–3354. 2008.PubMed/NCBI
4	Iturrioz X, El Messari S, De Mota N, et al: Functional dissociation between apelin receptor signaling and endocytosis: implications for the effects of apelin on arterial blood pressure. Arch Mal Coeur Vaiss. 100:704–708. 2007.PubMed/NCBI
5	Rastaldo R, Cappello S, Folino A, et al: Effect of apelin-apelin receptor system in postischaemic myocardial protection: a pharmacological postconditioning tool? Antioxid Redox Signal. 14:909–922. 2011. View Article : Google Scholar : PubMed/NCBI
6	Iturrioz X, Alvear-Perez R, De Mota N, et al: Identification and pharmacological properties of E339-3D6, the first nonpeptidic apelin receptor agonist. FASEB J. 24:1506–1517. 2010. View Article : Google Scholar : PubMed/NCBI
7	Shan PF, Lu Y, Cui RR, et al: Apelin attenuates the osteoblastic differentiation of vascular smooth muscle cells. PLoS One. 6:e179382011. View Article : Google Scholar : PubMed/NCBI
8	Roberts EM, Newson MJ, Pope GR, et al: Abnormal fluid homeostasis in apelin receptor knockout mice. J Endocrinol. 202:453–462. 2009. View Article : Google Scholar : PubMed/NCBI
9	Zhang Z, Yu B and Tao GZ: Apelin protects against cardiomyocyte apoptosis induced by glucose deprivation. Chin Med J. 122:2360–2365. 2009.PubMed/NCBI
10	Foussal C, Lairez O, Calise D, et al: Activation of catalase by apelin prevents oxidative stress-linked cardiac hypertrophy. FEBS Lett. 584:2363–2370. 2010. View Article : Google Scholar : PubMed/NCBI
11	Przewlocka-Kosmala M, Kotwica T, Mysiak A, et al: Reduced circulating apelin in essential hypertension and its association with cardiac dysfunction. J Hypertens. 29:971–979. 2011. View Article : Google Scholar : PubMed/NCBI
12	Khalili A, Khosravi MB and Nekooeian AA: The effects of aqueous extract of vaccinium arctostaphylos leaves on blood pressure in renal hypertensive rats. Iran Red Crescent Med J. 13:123–127. 2011.PubMed/NCBI
13	Zhou ZY, Yang ZH, Wang XH, et al: Increased expression of insulin-like growth factor-binding protein-3 is implicated in erectile dysfunction in two-kidney one-clip hypertensive rats after propranolol treatment. Asian J Androl. 13:851–855. 2011. View Article : Google Scholar : PubMed/NCBI
14	Lewis CJ, Gong H, Brown MJ, et al: Overexpression of β1-adrenoceptors in adult rat ventricular myocytes enhances CGP 12177A cardiostimulation: implications for ‘putative’ β4-adrenoceptor pharmacology. Br J Pharmacol. 141:813–824. 2004.
15	Glasser SP, Judd S, Basile J, et al: Prehypertension, racial prevalence and its association with risk factors: analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Am J Hypertens. 24:194–199. 2011. View Article : Google Scholar : PubMed/NCBI
16	Shahbaz AU, Sun Y, Bhattacharya SK, et al: Fibrosis in hypertensive heart disease: molecular pathways and cardioprotective strategies. J Hypertens. 28(Suppl 1): S25–S32. 2010. View Article : Google Scholar : PubMed/NCBI
17	Chen MM, Ashley EA, Deng DX, et al: Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation. 108:1432–1439. 2003. View Article : Google Scholar : PubMed/NCBI
18	Koguchi W, Kobayashi N, Takeshima H, et al: Cardioprotective effect of apelin-13 on cardiac performance and remodeling in end-stage heart failure. Circ J. 76:137–144. 2012. View Article : Google Scholar : PubMed/NCBI
19	Japp AG, Cruden NL, Barnes G, et al: Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure. Circulation. 121:1818–1827. 2010. View Article : Google Scholar : PubMed/NCBI
20	Simpkin JC, Yellon DM, Davidson SM, et al: Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemia-reperfusion injury. Basic Res Cardiol. 102:518–528. 2007. View Article : Google Scholar : PubMed/NCBI
21	Langelaan DN, Reddy T, Banks AW, et al: Structural features of the apelin receptor N-terminal tail and first transmembrane segment implicated in ligand binding and receptor trafficking. Biochim Biophys Acta. 1828.1471–1483. 2013.PubMed/NCBI
22	Dang VC and Christie MJ: Mechanisms of rapid opioid receptor desensitization, resensitization and tolerance in brain neurons. Br J Pharmacol. 165:1704–1716. 2012. View Article : Google Scholar : PubMed/NCBI
23	Yoshizawa T, Sakurai T, Kamiyoshi A, et al: Novel regulation of cardiac metabolism and homeostasis by the adrenomedullin-receptor activity-modifying protein 2 system. Hypertension. 61:341–351. 2013. View Article : Google Scholar : PubMed/NCBI
24	Shaul YD and Seger R: The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim Biophys Acta. 1773:1213–1226. 2007. View Article : Google Scholar : PubMed/NCBI
25	Hausenloy DJ and Yellon DM: New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. Cardiovasc Res. 61:448–460. 2004. View Article : Google Scholar : PubMed/NCBI
26	Rattazzi M, Bertacco E, Puato M, et al: Hypertension and vascular calcification: a vicious cycle? J Hypertens. 30:1885–1893. 2012. View Article : Google Scholar : PubMed/NCBI
27	Distefano G and Sciacca P: Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure. Ital J Pediatr. 38:412012. View Article : Google Scholar : PubMed/NCBI
28	Moser E, Kargl J, Whistler JL, et al: G protein-coupled receptor-associated sorting protein 1 regulates the postendocytic sorting of seven-transmembrane-spanning G protein-coupled receptors. Pharmacology. 86:22–29. 2010. View Article : Google Scholar
29	Pang H and Zhang P: Detection of the level of apelin during remodeling in hypertensive heart failure rats. Chin J Clinicians. 6:64–67. 2012.