Lokal Renin Anjiyotensin Sistemi: Fizyolojik ve Patofizyolojik Etkinliği

Öz

Abstract Local Renin-Angiotensin System: Physiologic and Pathophysiologic Effects Renin-angiotensin system (RAS) is one of the most important physiological systems which determines and protects the blood pressure by its effects on fluid and electrolyte balance. Since the first identification of renin molecule by Tigerstedt and Bergmann in 1898, the renin-angiotensin system (RAS) has been extensively studied. Angiotensin II, the most dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in (patho)biological states. In addition to the circulating (endocrine) RAS, the existence of RAS in varies tissues and diverse cells has also known. Recent studies have provided evidence of a complete, local RAS within cells, described as an 'intracrine' or intracellular system. The prorenin/ (Pro)renin receptor (PRR)/MAP kinase axis, the ACE2/Ang (1-7)/Mas receptor axis, and the Ang IV/AT II/insulin-regulated aminopeptidase axis also have recently been discovered. From the concept of local RAS, the effect of RAS on tissue and organ levels regardless from its systemic activity is understood. The evidence for physiological and pathophysiological effects of local RAS activities such as cell growth, differantion, proliferation, apoptosis, and formation of reactive oxygen products, tissue inflammation and fibrogenesis is gradually accumulated. Local actors other than the renin (chymase, tonin, i.e.) are thought to be more important in the regulation of local RAS. On the other hand, the members of the circulating RAS contribute to the activity of local RAS in tissues with the exception of brain. A better understanding of the autocrine and paracrine mechanisms involved in the local RASs might direct future organ-specific therapy. With this review, it was aimed to attract more attention to local RAS concept and its effects because of the complexity of the system and more widely use of the drugs affecting it.

Anahtar Kelimeler

• Renin-angiotensin system; angiotensin II; angiotensin-converting enzyme 2; receptor

Lokal Renin Anjiyotensin Sistemi: Fizyolojik ve Patofizyolojik Etkinliği

Öz

Türkçe Özet: Renin anjiyotensin sistemi (RAS), sıvı ve elektrolit dengesine yaptığı etkilerle kan basıncını belirleyen ve koruyan en önemli fizyolojik sistemlerdendir. İlk kez 1898 yılında Tigerstedt ve Bergmann\'ın renin molekülünü bulmasından bu yana RAS oldukça geniş bir biçimde çalışılmıştır. Anjiyotensin II (ATII), RAS\'ın en fonksiyonel molekülüdür ve birçok biyolojik ve patobiyolojik süreçte etkin rol oynar. Sistemik dolaşımdaki RAS aktivitesinden başka farklı hücre ve dokularda RAS varlığı ve etkinliği de gösterilmiştir. Yakın zamanda yapılan çalışmalar ile, intrakrin ya da “hücre içi” RAS olarak da bilinen lokal RAS\'ın etkinliği gösterilmiştir. Prorenin/Prorenin reseptör/MAP kinaz aksı, anjiyotensin dönüştürücü enzim 2 ADE2/Anjiyotensin (1-7)/Mas reseptör aksı ve anjiyotensin IV/ATII/insulin-regulated aminopeptidaz gibi süreçler yakın zamanda tanımlanmıştır. Lokal RAS varlığının, bulunduğu doku ya da organda; hücre büyümesi, farklılaşması, çoğalması, apoptozisi, reaktif oksijen ürünlerinin oluşumu, doku inflamasyonu ve fibrogenezdeki fizyolojik ve patofizyolojik rollerine dair kanıtlar giderek artmaktadır. Lokal RAS\'ta renin dışındaki faktörlerin (kimaz, tonin vb.) bu sistemin düzenlenmesinde daha baskın olduğu düşünülmektedir. Öte yandan, dolaşımdaki RAS üyeleri de, beyin dışındaki dokularda lokal RAS aktivitesine katkıda bulunmaktadır. Otokrin ve parakrin mekanizmaların daha iyi anlaşılmasıyla organ spesifik tedavide yeni ufukların açılması muhtemeldir. Bu derleme ile sistemin karmaşıklaşmasına ve bu sistemi etkileyen ilaçların yaygın kullanımı nedeniyle lokal RAS kavramı ve etkinliğine dikkat çekilmesi amaçlanmıştır.

Anahtar Kelimeler

• Renin-anjiotensin sistemi; anjiotensin II; anjiotensin dönüştürücü enzim 2; reseptör

Kaynakça

1. de Gaspare M, Call KJ. Inagami T, Wright JW. Unger T.
2. International union of pharmacology. XXIII. The angiotensin
3. II receptors. Phat-maco Rev 2t]titi;52[3}:4lj-T2,
4. Saris JJ. Derkit FH. Lamers JM. Saaena PR. Schalekamp
5. MA, Danser AH. Cardiomyu-cytes bind and activate native
6. prorcnin: role ol' soluble mannose (”J-phosphate receptors.
7. Hyper-tension 2001.37(2):7I0—5.
8. Vaajanen A. Vapaataio H. Local ocular renin-angiotensin

9. systemıa target for glaucoma therapy? Basic Clin Piran-mimi
10. To,-fimi 2t'll 1:109(4):2 I 7-24.
11. Clermont A. Bursell SE, Feener EP. Role of the angiotensin
12. ll type I receptor in the pathogenesis of diabetic retinopathy:
13. effects of blood pressure control and beyond. J' Hype—neni
14. Suppl 2006;24(I]:S?3—8Ü.
15. Kim HW. Kim .İl... Loc HK. Hur DY. Yurt [H, Kim SD.
16. Enalapril alters expression of key growth factors in
17. experimental diabetic retinopathy. Carr Eve Res 20091340 ”976-87.
18. El Hasnaoui-Saadani R. Piehon A. Marchanl D. Olivier P,
19. Launay T, Quidu P, Beaudry M, Duvallet A, Richalet JP,
20. Fawer F. Cerebral adaptations to chronic anemia in a model
21. ol' eryıhropoielin-tlel'ıcient mice exposed to hypoxia. Am J
22. Physioi Regui fotogr Camp Pity-riot 2009;296[3}1R30 1 -I I .
23. Kim JH, Kim JH, Yu YS, Cho CS. Kim KW. Blockade of
24. angiotensin [I attenuates lııı'EGF-metiiated blood-retinal
25. barrier breakdown in diabetic retinopathy. J Ceren Brand
26. Flaw Match 2009:29[3):62 l -3.
27. The EUCLID Study Group. EURODIAB Controlled Trial of
28. Lisinopril in Insulin—Dependent Diabetes Mellitus. twice: [993:35 “909323-31.
29. delie AK. Klein R. Porta M, Orchard T. Fuller J. Parving
30. HH. Bilous R. Chaturyedi N: DIRECT Programme Study
31. Group. DIRECT Programme Study Group. Effect of
32. candesartan on progression and regression ol' retinopathy in
33. type 2 diabetes [DIRECT-Protect 2]: a randomised placebo
34. controlled trial. Lurıı-e-r 2008” 8: 372t964'i): USS-93.
35. Matter M. Zinrnan B. Gardiner R, Suissa S. Sinaiku A. Strand T. Drummond K. Donnelly S. Goodyet P. Gublcr MC. Klein R. Renal and retinal effects of enalapril and losarlan in type I diabetes. N Eng J Med 2009;361t I ):4045I .
36. Ruggenenti P. lliey l. Filipponi M. Tadini S. Porna A. Garteva M. Ene—lordaehe B. Cravedi P. Trevisan R, Bossi A. Remuzzi G. Effect of trarıdolapril on regression of retinopathy in hypertensive patients with type 2 diabetes: a pre-specified analysis of the benedict trial. J Opiıthaimol 2010:201Ü:106384. doi: 10.1155J20l0t’106334.
37. Leung PS. The physiology of a local renin—angiotensin system in the pancreas. J Physio 200T:58'O{l]:3|-1
38. Tsung SW, Cheng CHK, Leung PS. The role of the pancreatic renin-angiotensin system in aeinar digestive enzyme secretion and in acute pancreatilis. Reg" Pepi zoom l9{3]|:213-9_
39. Lan T. Carlsson PO. Leung PS. Evidence for a beat angiotensin-generating system and dese—dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets. Diabetot'ogia 2004:4T(2):240—8.
40. Huang Z, Iansson L, Sjoholm A. Pancreatic islet blood flow is selectively enhanced by captoprii. irbesartan and pravastatin. and suppressed by palmitale. Bio-chem Bion-'iyi' Res Comm ED&F-%i |):26-32.
41. Abuissa H. Jones PG. Marso SP. O'Keefe JH. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes. J Am Colt Camii'ni 2(115;46(5):821-6.
42. Garcia P. Schwenaer S. Slotta IE. Scheuer C. Tami AE. Holstein .lH. Histing T. Burkhardt M. Pohlemann T. Menger MD. Inhibition of angiotensin-converting enzyme stimulates fracture healing and pcrioetea] callus formation — role of a loca] renin-angiotensin system. Br J Phat-mami 20|ş:]59(8):1t572—30.
43. Rejnmark L.. Vestergaard P. Mnsekilde L. Treatment with betabloekers, ACE inhibitors. and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. .ı" Hyperrens amenna).- 58 I-9.
44. Haznedaroglu IC. Tuncer S. Gursoy M. A local reninangiotensin systemin the bone marrow. Medic-ai Hypotheses ]996:46(6):50T-10.
45. Slrawn WB. Richmond RS. Ann TE, Gallagher PE, Ferrario CM, Renin-angiotensin system expression in rat bone marrow hacmatopoictic and stromal cells. Br Hammam 2m4;126[ I ): 120—6.
46. Haznedaroglu IC. Ozturk MA. Towards the understanding of the local hematopoietic bone marrow renin—angiotensin system. Int J Him-hem Celi Bini 2003'. 35(6): tŞ't—EŞ
47. Aksu S. Beyazit Y. Haznedaroglu IC. Kekilli M, Canpinar H. Misirlioğlu M. err A. Tuncer 5. Sayinalp N. Büyükaşik Y. Goker H. Ozcebe Ol. Enhanced expression of the local haematopoiclie bune marrow rcninangietcnsin system in polycythemia rubra vera. Jour-na of Informational Medi-'m Research 2005;33(6): sam.
48. Turgutalp w: Kayitin—r
49. Koca E. Haznedaroglu IC. Acar K. Beyazit Y. Aksu S. Misirlioglu M. Tuncer S. Sayinalp N. Ozcebe 01. Uner A. Reninangiotensirı system expression in the K562 human erythroleukaemic cell line. Jennie-i ofthe Renin-Angiotensin- Aidasremne System 200T; 3(3);l45-'i.
50. Koca E Haznedaroglu IC. Uncr A. Sayinaip N. Saglam AE. Goker H. Üzcebe Ül. Angiotensin converting enzyme expression of the lymphoma-associated macrophages in the ]yıuph nodes of Hodgkin’s disease Jnumm' of tire National Medica Association 200?;99l| l]: 1243-7.
51. Haznedaroglu [C. Beyazit "t". Pathobiological aspects of the local bone mm'row renin—angiotensin system: a review. Journal raf the RenEn-Angiotensin-Aidosterone System 2010: [(4)2054 3.
52. Fukuda D. Sara M. Role of bone marrow reninangiolensin system in the pathogenesis of atherosclerosis Pitamtomiogy and Therapeutics 2003: ] 18[2)1268-?o.
53. Giac'chelli G. Faloia E. Mariniello B. Sardu C. l['jatli C. Camili—oni MA. Guerricri M. Montero F. Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal anıl overweight subjects. Am J Hyperrms 2002:15(5):33 l-E.
54. Hattori 't'. Akimote K. Gross SS. Hatlori 5. Kasai K. Angiotensin-Il-indueed oxidative stress elicits hypoadipoııectinemitt in rats. Diabetaingia 20I ] :54(9):24'ı'5, dot: lDJm‘FisUUllS—Ul 1—2159—8.
55. lttndeleit-Dal'ım KA. Tikellis C. Reid CM. Johnston Cl. Cooper ME. Why blockade of renin—angiotensin system reduces the incidence of new-onset diabetes. J Hypenens 2005: 23(3):463-73.
56. Ogihara T. Nathan K. Fukui T. Fukiyarna K. chhima K. Oba K Sato T. Saruta T. Effects of eandesaı'tan compared with amlodipine in hypertensive patients with high cardiovascular risks: candcsartan anlihypcrtetısivc survival evaluation in Japan trial (CASE-J Eat]. i-t'yperrerrrion. 2008;? |(2}:393-8.
57. _ Levine IL. Cassell MD. Gross KW. Sigmund CD. Localization ot' renin expressing cells in the brain. by use of a REN-eGFP transgenic model. .F’irj-s'io.l Genomic: 2004: 1642):24il-6_
58. Contrepas A. Walker J. Koulakoff A. Franck KJ. Qadri F. Giaume C. Coron P. Schwartz CE. Nguyen G. A role of the [projrenin receptor in neuronal ceil differentiation. Am J Physio Rege ı'nt'egr Comp Physioi 2009129'i(2):R250ı ?.
59. Ardaillou R. Active fragments of Ang Ll: enzymatic pathways of synthesis and biological effects. Current Opinion in Nepiamiagy and Hyper-tension 199T:6(1i:28- 34.
60. Hou Ille-Ren. Wang Yan. Zhou Lin. Chen Kun. Tian Yi. Song Zhi. Boo J. Yang QD. Altered angiotensin— convening erısyme and ils effects on the brain in a rat model of Alzheimer disease. Chin Med . 2tttlt5;lll(22):2320—3.
61. Mao C. Shi L. Xu F, Zhang L. Xe 2. Development of fetal brain renin—angiotensin system and hypertension programmed in fetal origins. Frm.: Nettrohioı' 2009:87(4):252-63.
62. , Ellul J. Archer N. Foy CM. Poppe M. Boothby H. Nicholas H. Brown RG, Lovestone S. The effects of commonly prescribed drugs in patients with Alzheimer's disease on the rate ol' deterioration. J Neurol Neurosurg Psychiatry 2006;?8(3]:233-9.
63. Stragier B. Dc Bundel D. Surre S. Smolders [_ Vauquelin G. Dupont a, Michotte Y. Vanderheyıien P. involvement of insulin-regulated aminopeptidase in Ihe effects ofthe renin-angiotensin fragment angiotensin W: :1 review. Heart Failure Rev 20033 3(3):32 1—37.
64. Pereira MG. Beceri C. Oliveira M. Salgado MC. Garcia-Cairasco N. Costa-Nete CM. Inhibition of the Renin—Angiotensin System PrevenIs Seizures in A Rat Model ol' Epilepsy. Ciinimi Science 2010:] l9(l |]:4'i'i- 82.
65. , Herr D. Rodewald M. Fraser HM. Hack G. Konrad R. Kreienbel‘g R. Wulff C. Potential role of renin— angiotensinwsystcm for tumor angie-genesis in receptor negative breast cancer. Gynecol Onmi' 2003;|09{3):4|8- 25.
66. Tahmasehi M. Barker S. Puddefooı JR. Vinson GP. Localisation ol' renin-angiotensin system (RAS) components in breast. Br. Crt-near 200695“ ):67—4.