Vascular Functional Effects of the Apelinergic System

DEMİREL, Sadettin; Isbil Buyukcoskun, Naciye; ŞAHİNTÜRK, Serdar

doi:10.5336/pharmsci.2020-76153

Vascular Functional Effects of the Apelinergic System

Naciye İŞBİL, (Bursa Uludağ Üniversitesi, Tıp Fakültesi, Fnizyoloji Aabilim Dalı, Bursa, TÜRKİYE)

Serdar ŞAHİNTÜRK, (Bursa Uludağ Üniversitesi, Tıp Fakültesi, Fnizyoloji Aabilim Dalı, Bursa, TÜRKİYE)

Sadettin DEMİREL (Bursa Uludağ Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Bursa, TÜRKİYE)

Literatür Eczacılık Bilimleri Dergisi

1 1

Yıl: 2021 Cilt: 10 Sayı: 1 Sayfa Aralığı: 12 - 20 Metin Dili: İngilizce DOI: 10.5336/pharmsci.2020-76153 İndeks Tarihi: 01-10-2021

Vascular Functional Effects of the Apelinergic System

Öz:

The apelinergic system consists of apelin, elabela, andtheir common receptor apelin receptor (APJ). APJ is a G protein-coupled receptor. Apelin is the first discovered endogenous APJ ligand.Later, elabela was discovered and added to the system. Apelinergicsystem components have a widespread expression in the human body.The apelinergic system which plays a role in many physiological processes such as body-fluid homeostasis, energy metabolism, and regulation of cardiac contractility participates in the regulation ofvascular tone and blood pressure. Apelin and elabela, which have similar effects on vascular tone, differ in their effect mechanisms. APJ isexpressed in both vascular endothelial cells and vascular smooth muscle cells. This situation is important because it mediates the oppositeeffects in vascular tension. Apelin usually has a vasodilator effectthrough the activation of the endothelial nitric oxide synthase/nitricoxide (NO) pathway in physiological conditions. However, in the absence of a functional endothelium, apelin causes vasoconstriction.Elabela has a vasodilator effect similar to apelin, but it is thought thatNO has no role in the vasodilator effect of elabela. When apelin andelabela are administered peripherally, they usually lower blood pressure and exhibit an antihypertensive effect. Therefore, the apelinergicsystem has great potential to develop alternative agents for the treatment of hypertensive diseases such as essential hypertension and pulmonary hypertension. The half-lives of apelin and elabela are quiteshort, and current studies have focused on developing longer-actingapelinergic analogs. In this review, we focused on the vascular functional effects and effect mechanisms of the apelinergic system

Anahtar Kelime:

Apelinerjik Sistemin Vasküler Fonksiyonel Etkileri

Öz:

Apelinerjik sistem apelin, elabela ve bunların ortak reseptörü apelin reseptörü (APJ)’nden oluşur. APJ, G-proteini kenetli bir reseptördür. Apelin, ilk keşfedilen endojen APJ ligandıdır. Daha sonra ise elabela keşfedilerek sisteme eklenmiştir. Apelinerjik sistem elemanları insan vücudunda yaygın ekspresyona sahiptir. Vücut-sıvı homeostazı, enerji metabolizması ve kardiyak kontraktilitenin düzenlenmesi gibi birçok fizyolojik süreçte rolü olan apelinerjik sistem, damar tonusunun ve kan basıncının düzenlenmesine de katılır. Damar tonusu üzerine benzer etkileri olan apelin ve elabela, etki mekanizmasında farklılık gösterir. APJ, hem damar endotel hücrelerinde hem de damar düz kas hücrelerinde eksprese edilmektedir. Bu durum, damar geriminde karşıt etkilere aracılık etmesi nedeni ile önemlidir. Apelin, fizyolojik koşullarda genellikle endotelyal nitrik oksit sentaz/nitrik oksit (NO) yolağının aktivasyonu aracılığıyla vazodilatatör etki gösterir. Buna karşın apelin, fonksiyonel bir endotelin olmadığı durumlarda vazokonstriksiyona neden olmaktadır. Elabela da apeline benzer şekilde vazodilatatör etki gösterir fakat NO’nun, elabelanın vazodilatatör etkisinde hiçbir rolü olmadığı düşünülmektedir. Apelin ve elabela, periferik olarak uygulandıklarında, genellikle kan basıncını düşürür ve antihipertansif etki gösterirler. Bu nedenle apelinerjik sistem, esansiyel hipertansiyon ve pulmoner hipertansiyon gibi hipertansif hastalıkların tedavisi için alternatif ajanlar geliştirme konusunda büyük bir potansiyele sahiptir. Apelin ve elabelanın yarılanma ömürleri oldukça kısadır ve güncel çalışmalar, daha uzun etkili apelinerjik analoglar geliştirmeye odaklanmıştır. Bu derlemede, apelinerjik sistemin vasküler fonksiyonel etkileri ve etki mekanizmalarına odaklandık.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Reaux A, De Mota N, skultetyova I, Lenkei Z, El Messari s, Gallatz K, et al. Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. J Neurochem. 2001;77(4):1085-96. [Crossref] [PubMed]
2. Tatemoto K, Takayama K, Zou MX, Kumaki I, Zhang W, Kumano K, et al. The novel peptide apelin lowers blood pressure via a nitric oxidedependent mechanism. Regul Pept. 2001;99(2-3):87-92. [Crossref] [PubMed]
3. Taheri s, Murphy K, Cohen M, sujkovic E, Kennedy A, Dhillo W, et al. The effects of centrally administered apelin-13 on food intake, water intake and pituitary hormone release in rats. Biochem Biophys Res Commun. 2002;291(5):1208-12. [Crossref] [PubMed]
4. O'Carroll AM, Don AL, Lolait sJ. APJ receptor mRNA expression in the rat hypothalamic paraventricular nucleus: regulation by stress and glucocorticoids. J Neuroendocrinol. 2003;15(11):1095-101. [Crossref] [PubMed]
5. szokodi I, Tavi P, Földes G, Voutilainen-Myllylä s, Ilves M, Tokola H, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res. 2002;91(5):434-40. [Crossref] [PubMed]
6. Zhang L, Takara K, Yamakawa D, Kidoya H, Takakura N. Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy. Cancer sci. 2016;107(1):36-44. [Crossref] [PubMed] [PMC]
7. Bertrand C, Valet P, Castan-Laurell I. Apelin and energy metabolism. Front Physiol. 2015;6:115. [Crossref] [PubMed] [PMC]
8. Lv sY, Yang YJ, Qin YJ, Mo JR, Wang NB, Wang YJ, et al. Central apelin-13 inhibits food intake via the CRF receptor in mice. Peptides. 2012;33(1):132-8. [Crossref] [PubMed]
9. Gunes I, Kartal H, Dursun AD, sungu N, Polat Ys, Erkent FD, et al. Effects of apelin-13 on myocardial ischemia reperfusion injury in streptozotocine induced diabetic rats. Bratisl Lek Listy. 2018;119(6):348-54. [Crossref] [PubMed]
10. Lee DK, Cheng R, Nguyen T, Fan T, Kariyawasam AP, Liu Y, et al. Characterization of apelin, the ligand for the APJ receptor. J Neurochem. 2000;74(1):34-41. [PubMed]
11. Japp AG, Cruden NL, Amer DA, Li VK, Goudie EB, Johnston NR, et al. Vascular effects of apelin in vivo in man. J Am Coll Cardiol. 2008;52(11):908-13. [Crossref] [PubMed]
12. Ishida J, Hashimoto T, Hashimoto Y, Nishiwaki s, Iguchi T, Harada s, et al. Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. J Biol Chem. 2004;279(25):26274-9. [Crossref] [PubMed]
13. O'Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene. 1993;136(1-2):355-60. [PubMed]
14. Hosoya M, Kawamata Y, Fukusumi s, Fujii R, Habata Y, Hinuma s, et al. Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem. 2000;275(28):21061-7. [Crossref] [PubMed]
15. Xu J, Chen L, Jiang Z, Li L. Biological functions of Elabela, a novel endogenous ligand of APJ receptor. J Cell Physiol. 2018;233(9):6472-82. [Crossref] [PubMed]
16. Kleinz MJ, Davenport AP. Emerging roles of apelin in biology and medicine. Pharmacol Ther. 2005;107(2):198-211. [Crossref] [PubMed]
17. Zhang Y, Wang Y, Lou Y, Luo M, Lu Y, Li Z, et al. Elabela, a newly discovered APJ ligand: similarities and differences with Apelin. Peptides. 2018;109:23-32. [Crossref] [PubMed]
18. Jia YX, Lu ZF, Zhang J, Pan Cs, Yang JH, Zhao J, et al. Apelin activates L-arginine/nitric oxide synthase/nitric oxide pathway in rat aortas. Peptides. 2007;28(10):2023-9. [Crossref] [PubMed]
19. Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 1998;251(2):471-6. [Crossref] [PubMed]
20. Zhen EY, Higgs RE, Gutierrez JA. Pyroglutamyl apelin-13 identified as the major apelin isoform in human plasma. Anal Biochem. 2013;442(1):1-9. [Crossref] [PubMed]
21. Maguire JJ, Kleinz MJ, Pitkin sL, Davenport AP. [Pyr1]apelin-13 identified as the predominant apelin isoform in the human heart: vasoactive mechanisms and inotropic action in disease. Hypertension. 2009;54(3):598-604. [Crossref] [PubMed]
22. Huang Z, Luo X, Liu M, Chen L. Function and regulation of apelin/APJ system in digestive physiology and pathology. J Cell Physiol. 2019;234(6):7796-810. [Crossref] [PubMed]
23. Wysocka MB, Pietraszek-Gremplewicz K, Nowak D. The role of apelin in cardiovascular diseases, obesity and cancer. Front Physiol. 2018;9:557. [Crossref] [PubMed] [PMC]
24. Yang P, Read C, Kuc RE, Buonincontri G, southwood M, Torella R, et al. Elabela/toddler is an endogenous agonist of the apelin APJ receptor in the adult cardiovascular system, and exogenous administration of the peptide compensates for the downregulation of its expression in pulmonary arterial hypertension. Circulation. 2017;135(12):1160-73. [Crossref] [PubMed] [PMC]
25. Japp AG, Cruden NL, Barnes G, van Gemeren N, Mathews J, Adamson J, et al. Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure. Circulation. 2010;121(16):1818-27. [Crossref] [PubMed]
26. Barnes GD, Alam s, Carter G, Pedersen CM, Lee KM, Hubbard TJ, et al. sustained cardiovascular actions of APJ agonism during reninangiotensin system activation and in patients with heart failure. Circ Heart Fail. 2013;6(3):482-91. [PubMed]
27. shin K, Kenward C, Rainey JK. Apelinergic system structure and function. Compr Physiol. 2017;8(1):407-50. [Crossref] [PubMed] [PMC]
28. Yamaleyeva LM, shaltout HA, Varagic J. Apelin13 in blood pressure regulation and cardiovascular disease. Curr Opin Nephrol Hypertens. 2016;25(5):396-403. [Crossref] [PubMed]
29. Gurzu B, Petrescu BC, Costuleanu M, Petrescu G. Interactions between apelin and angiotensin II on rat portal vein. J Renin Angiotensin Aldosterone syst. 2006;7(4):212- 6. [Crossref] [PubMed]
30. salcedo A, Garijo J, Monge L, Fernández N, Luis García-Villalón A, sánchez Turrión V, et al. Apelin effects in human splanchnic arteries. Role of nitric oxide and prostanoids. Regul Pept. 2007;144(1-3):50-5. [Crossref] [PubMed]
31. Andersen Cu, Markvardsen LH, Hilberg O, simonsen u. Pulmonary apelin levels and effects in rats with hypoxic pulmonary hypertension. Respir Med. 2009;103(11):1663-71. [Crossref] [PubMed]
32. Huang P, Fan XF, Pan LX, Gao YQ, Mao sZ, Hu LG, et al. [Effect of apelin on vasodilatation of isolated pulmonary arteries in rats is concerned with the nitric oxide pathway]. Zhongguo Ying Yong sheng Li Xue Za Zhi. 2011;27(1):1-5. [PubMed]
33. Wang Z, Yu D, Wang M, Wang Q, Kouznetsova J, Yang R, et al. Elabela-apelin receptor signaling pathway is functional in mammalian systems. sci Rep. 2015;5:8170. [Crossref] [PubMed] [PMC]
34. Mughal A, sun C, O'Rourke sT. Activation of large conductance, calcium-activated potassium channels by nitric oxide mediates apelininduced relaxation of isolated rat coronary arteries. J Pharmacol Exp Ther. 2018;366(2):265-73. [Crossref] [PubMed] [PMC]
35. Zhong JC, Yu XY, Huang Y, Yung LM, Lau CW, Lin sG. Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice. Cardiovasc Res. 2007;74(3):388-95. [Crossref] [PubMed]
36. Japp AG, Newby DE. The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential. Biochem Pharmacol. 2008;75(10):1882-92. [Crossref] [PubMed]
37. Rastaldo R, Cappello s, Folino A, Losano G. Effect of apelin-apelin receptor system in postischaemic myocardial protection: a pharmacological postconditioning tool? Antioxid Redox signal. 2011;14(5):909-22. [Crossref] [PubMed]
38. Ladeiras-Lopes R, Ferreira-Martins J, LeiteMoreira AF. The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications. Arq Bras Cardiol. 2008;90(5):343-9. [Crossref] [PubMed]
39. Modgil A, Guo L, O'Rourke sT, sun C. Apelin13 inhibits large-conductance Ca2+-activated K+ channels in cerebral artery smooth muscle cells via a PI3-kinase dependent mechanism. PLos One. 2013;8(12):e83051. [Crossref] [PubMed] [PMC]
40. Katugampola sD, Maguire JJ, Matthewson sR, Davenport AP. [(125)I]-(Pyr(1))Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man. Br J Pharmacol. 2001;132(6):1255-60. [Crossref] [PubMed] [PMC]
41. Pitkin sL, Maguire JJ, Kuc RE, Davenport AP. Modulation of the apelin/APJ system in heart failure and atherosclerosis in man. Br J Pharmacol. 2010;160(7):1785-95. [Crossref] [PubMed] [PMC]
42. Wang LY, Zhang DL, Zheng JF, Zhang Y, Zhang QD, Liu WH. Apelin-13 passes through the ADMA-damaged endothelial barrier and acts on vascular smooth muscle cells. Peptides. 2011;32(12):2436-43. [Crossref] [PubMed]
43. Hashimoto T, Kihara M, Ishida J, Imai N, Yoshida s, Toya Y, et al. Apelin stimulates myosin light chain phosphorylation in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2006;26(6):1267-72. [Crossref] [PubMed]
44. Mughal A, sun C, OʼRourke sT. Apelin reduces nitric oxide-ınduced relaxation of cerebral arteries by ınhibiting activation of large-conductance, calcium-activated K channels. J Cardiovasc Pharmacol. 2018;71(4): 223-32. [Crossref] [PubMed] [PMC]
45. Lee DK, saldivia VR, Nguyen T, Cheng R, George sR, O'Dowd BF. Modification of the terminal residue of apelin-13 antagonizes its hypotensive action. Endocrinology. 2005;146(1):231-6. [PubMed]
46. Cheng X, Cheng Xs, Pang CC. Venous dilator effect of apelin, an endogenous peptide ligand for the orphan APJ receptor, in conscious rats. Eur J Pharmacol. 2003;470(3):171-5. [Crossref] [PubMed]
47. Najafipour H, soltani Hekmat A, Nekooian AA, Esmaeili-Mahani s. Apelin receptor expression in ischemic and non- ischemic kidneys and cardiovascular responses to apelin in chronic two-kidney-one-clip hypertension in rats. Regul Pept. 2012;178(1-3):43-50. [Crossref] [PubMed]
48. Charles CJ, Rademaker MT, Richards AM. Apelin-13 induces a biphasic haemodynamic response and hormonal activation in normal conscious sheep. J Endocrinol. 200;189(3):701-10. [Crossref] [PubMed]
49. Kagiyama s, Fukuhara M, Matsumura K, Lin Y, Fujii K, Iida M. Central and peripheral cardiovascular actions of apelin in conscious rats. Regul Pept. 2005;125(1-3):55-9. [Crossref] [PubMed]
50. Han X, Zhang DL, Yin DX, Zhang QD, Liu WH. Apelin-13 deteriorates hypertension in rats after damage of the vascular endothelium by ADMA. Can J Physiol Pharmacol. 2013;91(9):708-14. [Crossref] [PubMed]
51. Nagano K, Ishida J, unno M, Matsukura T, Fukamizu A. Apelin elevates blood pressure in ICR mice with L NAME induced endothelial dysfunction. Mol Med Rep. 2013;7(5):1371-5. [Crossref] [PubMed] [PMC]
52. Zhang F, sun HJ, Xiong XQ, Chen Q, Li YH, Kang YM, et al. Apelin-13 and APJ in paraventricular nucleus contribute to hypertension via sympathetic activation and vasopressin release in spontaneously hypertensive rats. Acta Physiol (Oxf). 2014;212(1):17-27. [Crossref] [PubMed]
53. Zhang Q, Yao F, Raizada MK, O'Rourke sT, sun C. Apelin gene transfer into the rostral ventrolateral medulla induces chronic blood pressure elevation in normotensive rats. Circ Res. 2009;104(12):1421-8. [Crossref] [PubMed] [PMC]
54. seyedabadi M, Goodchild AK, Pilowsky PM. site-specific effects of apelin-13 in the rat medulla oblongata on arterial pressure and respiration. Auton Neurosci. 2002;101(1-2):32- 8. [Crossref] [PubMed]
55. Yao F, Modgil A, Zhang Q, Pingili A, singh N, O'Rourke sT, et al. Pressor effect of apelin-13 in the rostral ventrolateral medulla: role of NAD(P)H oxidase-derived superoxide. J Pharmacol Exp Ther. 2011;336(2):372-80. [Crossref] [PubMed] [PMC]
56. Cudnoch-Jedrzejewska A, Gomolka R, szczepanska-sadowska E, Czarzasta K, Wrzesien R, Koperski L, et al. High-fat diet and chronic stress reduce central pressor and tachycardic effects of apelin in sprague-Dawley rats. Clin Exp Pharmacol Physiol. 2015;42(1):52-62. [Crossref] [PubMed] 57. Dai T, Ramirez-Correa G, Gao WD. Apelin increases contractility in failing cardiac muscle. Eur J Pharmacol. 2006;553(1-3):222-8. [Crossref] [PubMed] [PMC]
58. Zhong JC, Yu XY, Huang Y, Yung LM, Lau CW, Lin sG. Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice. Cardiovasc Res. 2007;74(3):388-95. [Crossref] [PubMed]
59. Zhong JC, Huang Y, Yung LM, Lau CW, Leung FP, Wong WT, et al. The novel peptide apelin regulates intrarenal artery tone in diabetic mice. Regul Pept. 2007;144(1-3):109-14. [Crossref] [PubMed]
60. Andersen Cu, Hilberg O, Mellemkjær s, Nielsen-Kudsk JE, simonsen u. Apelin and pulmonary hypertension. Pulm Circ. 2011;1(3):334-46. [Crossref] [PubMed] [PMC]
61. Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, et al. Design, characterization, and first-in-human study of the vascular actions of a novel biased apelin receptor agonist. Hypertension. 2015;65(4):834-40. [Crossref] [PubMed] [PMC]
62. Iturrioz X, Alvear-Perez R, De Mota N, Franchet C, Guillier F, Leroux V, et al. Identification and pharmacological properties of E339-3D6, the first nonpeptidic apelin receptor agonist. FAsEB J. 2010;24(5):1506-17. [Crossref] [PubMed]
63. Gerbier R, Alvear-Perez R, Margathe JF, Flahault A, Couvineau P, Gao J, et al. Development of original metabolically stable apelin-17 analogs with diuretic and cardiovascular effects. FAsEB J. 2017;31(2):687-700. [Crossref] [PubMed]
64. Chng sC, Ho L, Tian J, Reversade B. ELABELA: a hormone essential for heart development signals via the apelin receptor. Dev Cell. 2013;27(6):672-80. [Crossref] [PubMed]
65. Pauli A, Norris ML, Valen E, Chew GL, Gagnon JA, Zimmerman s, et al. Toddler: an embryonic signal that promotes cell movement via Apelin receptors. science. 2014;343(6172):1248636. [Crossref] [PubMed] [PMC]
66. Perjés Á, Kilpiö T, ulvila J, Magga J, Alakoski T, szabó Z, et al. Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart. Basic Res Cardiol. 2016;111(1):2. [PubMed]
67. sato T, sato C, Kadowaki A, Watanabe H, Ho L, Ishida J, et al. ELABELA-APJ axis protects from pressure overload heart failure and angiotensin II-induced cardiac damage. Cardiovasc Res. 2017;113(7):760-9. [Crossref] [PubMed]
68. Chun HJ, Ali ZA, Kojima Y, Kundu RK, sheikh AY, Agrawal R, et al. Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. J Clin Invest. 2008;118(10):3343-54. [PubMed] [PMC]
69. Murza A, sainsily X, Coquerel D, Côté J, Marx P, Besserer-Offroy É, et al. Discovery and structure-activity relationship of a bioactive fragment of ELABELA that modulates vascular and cardiac functions. J Med Chem. 2016;59(7):2962-72. [Crossref] [PubMed]
70. Ho L, van Dijk M, Chye sTJ, Messerschmidt DM, Chng sC, Ong s, et al. ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice. science. 2017;357(6352):707-13. [Crossref] [PubMed]
71. Li Y, Yang X, Ouyang s, He J, Yu B, Lin X, et al. Declined circulating Elabela levels in patients with essential hypertension and its association with impaired vascular function: a preliminary study. Clin Exp Hypertens. 2020;42(3):239-43. [Crossref] [PubMed]

APA	Isbil Buyukcoskun N, ŞAHİNTÜRK S, DEMİREL S (2021). Vascular Functional Effects of the Apelinergic System. , 12 - 20. 10.5336/pharmsci.2020-76153
Chicago	Isbil Buyukcoskun Naciye,ŞAHİNTÜRK Serdar,DEMİREL Sadettin Vascular Functional Effects of the Apelinergic System. (2021): 12 - 20. 10.5336/pharmsci.2020-76153
MLA	Isbil Buyukcoskun Naciye,ŞAHİNTÜRK Serdar,DEMİREL Sadettin Vascular Functional Effects of the Apelinergic System. , 2021, ss.12 - 20. 10.5336/pharmsci.2020-76153
AMA	Isbil Buyukcoskun N,ŞAHİNTÜRK S,DEMİREL S Vascular Functional Effects of the Apelinergic System. . 2021; 12 - 20. 10.5336/pharmsci.2020-76153
Vancouver	Isbil Buyukcoskun N,ŞAHİNTÜRK S,DEMİREL S Vascular Functional Effects of the Apelinergic System. . 2021; 12 - 20. 10.5336/pharmsci.2020-76153
IEEE	Isbil Buyukcoskun N,ŞAHİNTÜRK S,DEMİREL S "Vascular Functional Effects of the Apelinergic System." , ss.12 - 20, 2021. 10.5336/pharmsci.2020-76153
ISNAD	Isbil Buyukcoskun, Naciye vd. "Vascular Functional Effects of the Apelinergic System". (2021), 12-20. https://doi.org/10.5336/pharmsci.2020-76153

APA	Isbil Buyukcoskun N, ŞAHİNTÜRK S, DEMİREL S (2021). Vascular Functional Effects of the Apelinergic System. Literatür Eczacılık Bilimleri Dergisi, 10(1), 12 - 20. 10.5336/pharmsci.2020-76153
Chicago	Isbil Buyukcoskun Naciye,ŞAHİNTÜRK Serdar,DEMİREL Sadettin Vascular Functional Effects of the Apelinergic System. Literatür Eczacılık Bilimleri Dergisi 10, no.1 (2021): 12 - 20. 10.5336/pharmsci.2020-76153
MLA	Isbil Buyukcoskun Naciye,ŞAHİNTÜRK Serdar,DEMİREL Sadettin Vascular Functional Effects of the Apelinergic System. Literatür Eczacılık Bilimleri Dergisi, vol.10, no.1, 2021, ss.12 - 20. 10.5336/pharmsci.2020-76153
AMA	Isbil Buyukcoskun N,ŞAHİNTÜRK S,DEMİREL S Vascular Functional Effects of the Apelinergic System. Literatür Eczacılık Bilimleri Dergisi. 2021; 10(1): 12 - 20. 10.5336/pharmsci.2020-76153
Vancouver	Isbil Buyukcoskun N,ŞAHİNTÜRK S,DEMİREL S Vascular Functional Effects of the Apelinergic System. Literatür Eczacılık Bilimleri Dergisi. 2021; 10(1): 12 - 20. 10.5336/pharmsci.2020-76153
IEEE	Isbil Buyukcoskun N,ŞAHİNTÜRK S,DEMİREL S "Vascular Functional Effects of the Apelinergic System." Literatür Eczacılık Bilimleri Dergisi, 10, ss.12 - 20, 2021. 10.5336/pharmsci.2020-76153
ISNAD	Isbil Buyukcoskun, Naciye vd. "Vascular Functional Effects of the Apelinergic System". Literatür Eczacılık Bilimleri Dergisi 10/1 (2021), 12-20. https://doi.org/10.5336/pharmsci.2020-76153