The renin-angiotensin system: New insight into old therapies

Current Medicinal Chemistry

Volumn 20, Issue 10, 2013, Pages 1313-1322

  Ramirez Sanchez M ^a   Prieto, I ^a   Wangensteen, R ^a   Banegas, I ^a   Segarra, A B ^a   Villarejo, A B ^a   Vives, F ^b   Cobo, J ^a   De Gasparo, M ^c  

^a UNIVERSITY OF JAÉN   (Spain)

^b UNIVERSITY OF GRANADA   (Spain)

^c Cardiovascular and Metabolic Syndrome Adviser   (Switzerland)

Author keywords

Angiotensin Receptor Blockers; Angiotensin Converting Enzyme Inhibitors; Angiotensinases; Beta Blockers; Brain Asymmetry; Renin angiotensin system

Indexed keywords

ALISKIREN; ANALGESIC AGENT; ANGIOTENSIN; ANGIOTENSIN [1-7]; ANGIOTENSIN [1-9]; ANGIOTENSIN [2-10]; ANGIOTENSIN CONVERTING ENZYME 2; ANGIOTENSIN DERIVATIVE; ANGIOTENSIN II [3-8]; ANGIOTENSIN III; ANGIOTENSIN RECEPTOR; ANGIOTENSIN RECEPTOR ANTAGONIST; ANGIOTENSINASE; ANGIOTENSINASE ACTIVATOR; ANGIOTENSINASE INHIBITOR; ANTIDEPRESSANT AGENT; ANTIHYPERTENSIVE AGENT; ASPARTYL AMINOPEPTIDASE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CAPTOPRIL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EC 33; ENALAPRIL; ENZYME ACTIVATOR; ENZYME INHIBITOR; GLUTAMYL AMINOPEPTIDASE; PEPTIDE; RB 150; RESORCINOLNAPHTALEIN; UNCLASSIFIED DRUG; XANTHENONE;

ALZHEIMER DISEASE; ARTICLE; BRAIN ASYMMETRY; EPILEPSY; ESSENTIAL HYPERTENSION; HUMAN; ISCHEMIA; NONHUMAN; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM;

ANGIOTENSIN RECEPTOR ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; ANGIOTENSINS; ANTIHYPERTENSIVE AGENTS; ENDOPEPTIDASES; HUMANS; HYPERTENSION; PROTEASE INHIBITORS; RECEPTORS, ANGIOTENSIN; RENIN-ANGIOTENSIN SYSTEM;

EID: 84877942713     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867311320100008     Document Type: Article

References (85)

1. Tigerstedt R. Bergman P.G. Niere und Kreislauf. Skandinavisches Archiv. fur Physiologie 1898 8 223-271.
2. Robertson J.I.S. In: The Renin-Angiotensin System Robertson J.I.S. and Nicholls M.G. Eds. Mosby: London 1993 Vol. 1 pp. 1.1-1.18.
3. Jan Danser A.H. Batenburg W.W. van Esch J.H. Prorenin and the (pro)renin receptor-an update. Nephrol. Dial. Transplant. 2007 22(5) 1288-1292.
4. Nguyen G. Delarue F. Burckle C. Bouzhir L. Giller T. Sraer J.D. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J. Clin. Invest. 2002 109(11) 1417-1427. (Pubitemid 34596167)
5. Goodfriend T.L. In: The Renin-Angiotensin System Robertson J.I.S. and Nicholls M.G. Eds. Mosby: London 1993 Vol. 1 pp. 11.1-11.5.
6. Erdos E.G. Conversion of angiotensin I to angiotensin II. Am. J. Med. 1976 60(6) 749-759.
7. Troyanovskaya M. Jayaraman G. Song L. Healy D.P. Aminopeptidase-A. I. CDNA cloning and expression and localization in rat tissues. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000 278(2) R413-R424. (Pubitemid 30129632)
8. Wilk S. Wilk E. Magnusson R.P. Purification characterization and cloning of a cytosolic aspartyl aminopeptidase. J. Biol. Chem. 1998 273(26) 15961-15970. (Pubitemid 28311361)
9. Banegas I. Prieto I. Vives F. Alba F. de Gasparo M. Segarra A.B. Hermoso F. Duran R. Ramirez M. Brain aminopeptidases and hypertension. J. Renin Angiotensin Aldosterone Syst. 2006 7(3) 129-134. (Pubitemid 44740946)
10. Clarke N.E. Turner A.J. Angiotensin-converting enzyme 2: the first decade. Int. J. Hypertens. 2012 2012 307315.
11. Speth R.C. Karamyan V.T. The significance of brain aminopeptidases in the regulation of the actions of angiotensin peptides in the brain. Heart Fail. Rev. 2008 13(3) 299-309.
12. Wright J.W. Harding J.W. Brain renin-angiotensin-a new look at an old system. Prog. Neurobiol. 2011 95(1) 49-67.
13. Marc Y. Llorens-Cortes C. The role of the brain reninangiotensin system in hypertension: implications for new treatment. Prog. Neurobiol. 2011 95(2) 89-103.
14. Bader M. Ganten D. Update on tissue renin-angiotensin systems. J. Mol. Med. (Berl). 2008 86(6) 615-621.
15. Fyhrquist F. Saijonmaa O. Renin-angiotensin system revisited. J. Intern. Med. 2008 264(3) 224-236.
16. Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am. J. Cardiol. 2002 89(2A) 3A-9A.
17. Kaji K. Yoshiji H. Ikenaka Y. Noguchi R. Aihara Y. Shirai Y. Douhara A. Fukui H. Possible Involvement of Angiogenesis in Chronic Liver Diseases: Interaction Among Renin-Angiotensin-Aldosterone System Insulin Resistance and Oxidative Stress. Curr. Med. Chem. 2012 19(12) 1889-1898.
18. Kagami S. Involvement of glomerular renin-angiotensin system (RAS) activation in the development and progression of glomerular injury. Clin. Exp. Nephrol. 2012 16(2) 214-220.
19. Kruegel J. Rubel D. Gross O. Alport syndrome-insights from basic and clinical research. Nat. Rev. Nephrol. 2012 doi: 10.1038/nrneph.2012.259.
20. Wright J.W. Yamamoto B.J. Harding J.W. Angiotensin receptor subtype mediated physiologies and behaviors: new discoveries and clinical targets. Prog. Neurobiol. 2008 84 157-181.
21. Blair-West J.R. Coghlan J.P. Denton D.A. Fei D.T. Hardy K.J. Scoggins B.A. Wright R.D. A dose-response comparison of the actions of angiotensin II and angiotensin III in sheep. J. Endocrinol. 1980 87(3) 409-417. (Pubitemid 11197666)
22. Goodfriend T.L. Peach M.J. Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin-angiotensin system. Circ. Res. 1975 36(6 Suppl 1) 38-48.
23. Yatabe J. Yoneda M. Yatabe M.S. Watanabe T. Felder R.A. Jose P.A. Sanada H. Angiotensin III stimulates aldosterone secretion from adrenal gland partially via angiotensin II type 2 receptor but not angiotensin II type 1 receptor. Endocrinology 2011 152(4) 1582-1588.
24. Li Q. Feenstra M. Pfaffendorf M. Eijsman L. van Zwieten P.A. Comparative vasoconstrictor effects of angiotensin II III and IV in human isolate saphenous vein. J. Cardiovasc. Pharmacol. 1997 29 451-456. (Pubitemid 27212747)
25. de Gasparo M. Whitebread S. Bottari S.P. Levens N.R. Heterogeneity of angiotensin receptor subtypes. In: Medicinal Chemistry of the Renin Angiotensin System Timmermans PBMWM Wexler RR editors. Elsevier Science BV 1994 pp 269-294.
26. Garcia-Sainz J.A. Martinez-Alfaro M. Romero-Avila M.T. Gonzalez-Espinosa C. Characterization of the AT1 angiotensin II receptor expressed in guinea pig liver. J. Endocrinol. 1997 154 133-138. (Pubitemid 27304356)
27. Ruiz-Ortega M. Lorenzo O. Egido J. Angiotensin III upregulates genes involved in kidney damage in mesangial cells and renal interstitial fibroblast. Kidney Int. 1998 Suppl. 68 S41-S45. (Pubitemid 28531774)
28. Pelegrini-da-Silva A. Rosa E. Guethe L.M. Juliano M.A. Prado W.A. Martins. A.R. Angiotensin III modulates the nociceptive control mediated by the periaqueductal gray matter. Neuroscience 2009 164(3) 1263-1273.
29. Wright J.W. Mizutani S. Murray C.E. Amir H.Z. Harding J.W. Aminopeptidase-induced elevations and reductions in blood pressure in the spontaneously hypertensive rat. J. Hypertens. 1990 8 969-974. (Pubitemid 20368621)
30. Coleman J.K. Krebs LT. Hamilton T.A. Ong B. Lawrence K.A. Sardinia M.F. Harding J.W. Wright J.W. Autoradiographic identification of kidney angiotensin IV binding sites and angiotensin IV-induced renal cortical blood flow changes in rats. Peptides 1998 19(2) 269-277. (Pubitemid 28097926)
31. Wright J.W. Harding J.W. The brain angiotensin system and extracellular matrix molecules in neural plasticity learning and memory. Prog. Neurobiol. 2004 72 263-293. (Pubitemid 38609580)
32. Chai S.Y. Fernando R. Peck G. Ye S.Y. Mendelsohn F.A. Jenkins T.A. Albiston A.L. The angiotensin IV/AT4 receptor. Cell. Mol. Life Sci. 2004 61(21) 2728-2737.
33. Beyer C.E. Dwyer J.M. Platt B.J. Neal S. Luo B. Ling H.P. Lin Q. Mark R.J. Rosenzweig-Lipson S. Schechter L.E. Angiotensin IV elevates oxytocin levels in the rat amygdala and produces anxiolytic-like activity through subsequent oxytocin receptor activation. Psychopharmacology (Berl). 2010 209(4) 303-311.
34. Esteban V. Ruperez M. Sanchez-Lopez E. Rodriguez-Vita J. Lorenzo O. Demaegdt H. Vanderheyden P. Egido J. Ruiz-Ortega M. Angiotensin IV activates the nuclear transcription factor-kappaB and related proinflammatory genes in vascular smooth muscle cells. Circ. Res. 2005 96(9) 965-973. (Pubitemid 40712796)
35. Yang H. Zeng X.J. Wang H.X. Zhang L.K. Dong X.L. Guo S. Du J. Li H.H. Tang C.S. Angiotensin IV protects against angiotensin II-induced cardiac injury via AT4 receptor. Peptides 2011 32(10) 2108-2115.
36. Wong Y.C. Sim M.K. Lee K.O. Des-aspartate-angiotensin-I and angiotensin IV improve glucose tolerance and insulin signalling in diet-induced hyperglycaemic mice. Biochem. Pharmacol. 2011 82(9) 1198-1208.
37. Schindler C. Bramlage P. Kirch W. Ferrario C.M. Role of the vasodilator peptide angiotensin-(1-7) in cardiovascular drug therapy. Vasc. Health Risk Manag. 2007 3(1) 125-37. (Pubitemid 46860722)
38. Schiavone M.T. Khosla M.C. Ferrario C.M. Angiotensin-[1-7]: evidence for novel actions in the brain. J. Cardiovasc. Pharmacol. 1990 16 Suppl 4 S19-24.
39. Ferreira A.J. Murca T.M. Fraga-Silva R.A. Castro C.H. Raizada M.K. Santos R.A. New cardiovascular and pulmonary therapeutic strategies based on the Angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor axis. Int. J. Hypertens. 2012 2012 147825.
40. Brzozowski T. Ptak-Belowska A. Kwiecien S. Krzysiek-Maczka G. Strzalka M. Drozdowicz D. Pardo R. Olszanecki R. Korbut R. Konturek S.J. Pawlik W.W. Novel concept in the mechanism of injury and protection of gastric mucosa: role of renin-angiotensin system and active metabolites of angiotensin. Curr. Med. Chem. 2012 19(1) 55-62.
41. Kaparianos A. Argyropoulou E. Local Renin-Angiotensin II Systems Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases Pulmonary Hypertension and Acute Respiratory Distress Syndrome. Curr. Med. Chem. 2011 18(23) 3506-3515.
42. Hernandez-Prada J.A. Ferreira A.J. Katovich M.J. Shenoy V. Qi Y. Santos R.A. Castellano R.K. Lampkins A.J. Gubala V. Ostrov D.A. Raizada M.K. Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents. Hypertension 2008 51(5) 1312-1317. (Pubitemid 351555943)
43. Ocaranza M.P. Jalil J.E. Protective Role of the ACE2/Ang-(1-9) Axis in Cardiovascular Remodeling. Int. J. Hypertens. 2012 2012 594361.
44. Prieto I. Hermoso F. de Gasparo M. Vargas F. Alba F. Segarra A.B. Ramirez M. Angiotensinase activities in the kidney of renovascular hypertensive rats. Peptides 2003 24 755-760. (Pubitemid 36930007)
45. Mustafa M.R. Dharmani M. Kunheen N.K. Sim M.K. Effects of des-aspartate-angiotensin I on the actions of angiotensin III in the renal and mesenteric vasculature of normo-and hypertensive rats. Regul. Pept. 2004 120 15-22. (Pubitemid 38726187)
46. Sim M.K. Radhakrishnan R. Novel central action of des-Aspangiotensin I. Eur. J. Pharmacol. 1994 257 R1-3.
47. Wong Y.C. Sim M.K. Lee K.O. Des-aspartate-angiotensin-I and angiotensin IV improve glucose tolerance and insulin signalling in diet-induced hyperglycaemic mice. Biochem. Pharmacol. 2011 82(9) 1198-208.
48. Whitebread S. Mele M. Kamber B. de Gasparo M. Preliminary biochemical characterization of two angiotensin II receptor subtypes. Biochem. Biophys. Res. Commun. 1989 163 284-291. (Pubitemid 19227303)
49. Harding J.W. Cook V.I. Miller-Wing A.V. Hanesworth J.M. Sardinia M.F. Hall K.L. Stobb J.W. Swanson G.N. Coleman J.K. Wright J.W. et al. Identification of an AII (3-8) AIV binding site in guinea pig hippocampus. Brain Res. 1992 583 340-343.
50. Santos R.A. Simoes e Silva A.C. Maric C. Silva D.M.R. Machado R.P. de Buhr I. Heringer-Walther S. Pinheiro S.V.B. Lopes M.T. Bader M. Mendes E.P. Lemos V.S. Campagnole-Santos M.J. Schultheiss H.P. Speth R. Walther T. Angiotensin-(1-7) is an endogenous ligand for the G-protein coupled receptor Mas. Proc. Natl. Acad. Sci. U. S. A. 2003 100 8258-8263 (Pubitemid 36842532)
51. de Gasparo M. Catt K.J. Inagami T. Wright J.W. Unger T. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol. Rev. 2000 52 415-472.
52. Flores-Munoz N. J. Smith C. Haggerty G. Milligan G. Nicklin S.A. Angiotensin1-9 antagonises pro-hypertrophic signalling in cardiomyocytes via the angiotensin type 2 receptor J. Physiol. 2011 589(4) 939-951.
53. Steckelings U.M. Larhed M. Hallberg A. Widdop R.E. Jones E.S. Wallinder C. Namsolleck P. Dahlof B. Unger T. Nonpeptide AT2-receptor agonists. Curr. Opin. Pharmacol. 2011 11(2) 187-192.
54. Albiston A.L. Mcdowall S.G. Matsacos D. Sim P. Clune E. Mustafa T. Lee J. Mendelsohn F.A. Simpson R.J. Connolly L.M. Chai S.Y. Evidence that the angiotensin IV (AT4) receptor is the enzyme insulin-regulated aminopeptidase. J. Biol. Chem. 2001 276(52) 48623-48626.
55. Stragier B. De Bundel D. Sarre S. Smolders I. Vauquelin G. Dupont A. Michotte Y. Vanderheyden P. Involvement of insulin-regulated aminopeptidase in the effects of the renin-angiotensin fragment angiotensin IV: a review. Heart Fail. Rev. 2008 13(3) 321-337.
56. Gard P.R. Cognitive-enhancing effects of angiotensin IV. BMC Neurosci. 2008 9 Suppl.2 S15.
57. Banegas I. Prieto I. Vives F. Alba F. de Gasparo M. Duran R. Segarra A.B. Ramirez M. Lateralized response of oxytocinase activity in the medial prefrontal cortex of a unilateral rat model of Parkinson's disease. Behav. Brain Res. 2010 213(2) 328-331.
58. Ramirez M. Banegas I. Segarra A.B. Wangensteen R. de Gasparo M. Duran R. Vives F. Martinez A. Alba F. Prieto I. Bilateral Distribution of Oxytocinase Activity in the Medial Prefrontal Cortex of Spontaneously Hypertensive Rats with Experimental Hemiparkinsonism Mechanisms in Parkinson's Disease -Models and Treatments 2012 Dr. Juliana Dushanova (Ed.) ISBN: 978-953-307-876-2 http://www.intechopen.com/books/mechanisms-in-parkinson-sdisease-models-and- treatments/bilateral-distribution-ofoxytocinase-activity-in-the-medial- prefrontal-cortex-ofspontaneously-hype.
59. Wright J.W. Harding J.W. The angiotensin AT4 receptor subtype as a target for the treatment of memory dysfunction associated with Alzheimer's disease. J. Renin Angiotensin Aldosterone Syst. 2008 9(4) 226-237.
60. Ferdinand K.C. Update in pharmacologic treatment of hypertension. Cardiol. Clin. 2001 19 279-294. (Pubitemid 32500065)
61. Cobo J. Nogueras M. de la Torre J.M. Ramirez M. Prieto I. Segarra A.B. Pyrimido [45-e][14] diazepines and its influence in the aspartyl aminopeptidase activity. 8th Spanish-Italian Symposium on Organic Chemistry. 2010 July 3-6. Padova. Italy.
62. Zhenfeng Zheng. Huilan Shi. Junya Jia. Dong Li. Shan Lin. A systematic review and meta-analysis of aliskiren and angiotensin receptor blockers in the management of essential hypertension. J. Renin Angiotensin Aldosterone Syst. 2011 12(2) 102-112.
63. Luque M. Martin P. Martell N. Fernandez C. Brosnihan K.B. Ferrario C.M. Effects of captopril related to increased levels of prostacyclin and angiotensin-(1-7) in essential hypertension. J. Hypertens. 1996 14(6) 799-805. (Pubitemid 26187416)
64. Villarejo A.B. Segarra A.B. Ramirez M. Banegas I. Wangensteen R. de Gasparo M. Cobo J. Alba F. Vives F. Prieto I. Angiotensinase and vasopressinase activities in hypothalamus plasma and kidney after inhibition of angiotensin-converting enzyme: basis for a new working hypothesis. Horm. Metab. Res. 2012 44 152-154.
65. Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab. 2004 30(6) 487-496. (Pubitemid 40070350)
66. de Kloet A.D. Krause E.G. Kim D.H. Sakai R.R. Seeley R.J. Woods S.C. The effect of angiotensin-converting enzyme inhibition using captopril on energy balance and glucose homeostasis. Endocrinology 2009 150(9) 4114-4123.
67. Fernando R.N. Albiston A.L. Chai S.Y. The insulin-regulated aminopeptidase IRAP is colocalised with GLUT4 in the mouse hippocampus-potential role in modulation of glucose uptake in neurones? Eur. J. Neurosci. 2008 28(3) 588-598. (Pubitemid 352040410)
68. Albiston A.L. Yeatman H.R. Pham V. Fuller S.J. Diwakarla S. Fernando R.N. Chai S.Y. Distinct distribution of GLUT4 and insulin regulated aminopeptidase in the mouse kidney. Regul. Pept. 2011 166(1-3) 83-89.
69. Bogan J.S. Regulation of Glucose Transporter Translocation in Health and Diabetes. Annu. Rev. Biochem. 2012 81 507-532.
70. Segarra A.B. Prieto I. Banegas I. Villarejo A.B. Wangensteen R. de Gasparo M. Vives F. Ramirez-Sanchez M. Asymmetrical effect of captopril on the angiotensinase activity in frontal cortex and plasma of the spontaneously hypertensive rats: Expanding the model of neuroendocrine integration. Behav. Brain Res. 2012 230 423-427.
71. Bernard C. 1867. Lecture on the physiology of the heart and its connections with the brain delivered at the Sorbonne the 27th March 1865. Tr. By J.S. Morel Savannah Purse.
72. Thayer J.F. Lane R.D. A model of neurovisceral integration in emotion regulation and dysregulation. J. Affect. Disord. 2000 61 201-216. (Pubitemid 32119267)
73. Thayer J.F. Lane R.D. Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci. Biobehav. Rev. 2009 33 81-88.
74. Segarra A.B. Prieto I. Banegas I. Villarejo A.B. Wangensteen R. de Gasparo M. Vives F. Ramirez-Sanchez M. The brainheart connection: frontal cortex and left ventricle angiotensinase activities in control and captopril treated hypertensive rats. A bilateral study. Int. J. Hypertens. 2013 (in press).
75. Foster P.S. Harrison D.W. Magnitude of cerebral asymmetry at rest: covariation with baseline cardiovascular activity. Brain Cogn. 2006 61 286-297.
76. Braszko J.J. Karwowska-Polecka W. Halicka D. Gard P.R. Captopril and enalapril improve cognition and depressed mood in hypertensive patients. J. Basic Clin. Physiol. Pharmacol. 2003 14 323-343. (Pubitemid 38679252)
77. Prickaerts J. Raaijmakers W. Blokland A. Effects of myocardial infarction and captopril therapy on anxiety-related behaviors in the rat. Physiol. Behav. 1996 60 43-50. (Pubitemid 126335851)
78. Papousek I. Murhammer D. Schulter G. Intra-and interindividual differences in lateralized cognitive performance and asymmetrical EEG activity in the frontal cortex. Brain Cogn. 2011 75 225-231.
79. Sukumaran V. Veeraveedu P.T. Gurusamy N. Yamaguchi K. Lakshmanan A.P. Ma M. Suzuki K. Kodama M. Watanabe K. Cardioprotective effects of telmisartan against heart failure in rats induced by experimental autoimmune myocarditis through the modulation of angiotensin-converting enzyme-2/angiotensin 1-7/mas receptor axis. Int. J. Biol. Sci. 2011 7(8) 1077-1092.
80. Agata J. Ura N. Yoshida H. Shinshi Y. Sasaki H. Hyakkoku M. Taniguchi S. Shimamoto K. Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensinconverting enzyme. Hypertens. Res. 2006 29(11) 865-874. (Pubitemid 46062117)
81. Zong W.N. Yang X.H. Chen X.M. Huang H.J. Zheng H.J. Qin X.Y. Yong Y.H. Cao K. Huang J. Lu X.Z. Regulation of angiotensin-(1-7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure. Acta Pharmacol. Sin. 2011 32(11) 1345-1350.
82. Dedeoglu I.O. Springate J.E. Effect of nitric oxide inhibition on kidney function in experimental renovascular hypertension. Clin. Exp. Hypertens. 2001 23 267-275. (Pubitemid 32374607)
83. Vilas-Boas W.W. Ribeiro-Oliveira A. Ribeiro Rda C. Vieira R.L. Almeida J. Nadu A.P. Simoes e Silva A.C. Santos R.A. Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients. World J. Gastroenterol. 2008 14(44) 6824-6830.
84. Igase M. Yokoyama H. Ferrario C.M. Attenuation of hypertension-mediated glomerulosclerosis in conjunction with increased angiotensin (1-7). Ther. Adv. Cardiovasc. Dis. 2011 5(6) 297-304.
85. Ramirez M. Segarra A.B. Villarejo A.B. Banegas I Wangensteen R. Vives F. Prieto I. Angiotensinase activity in hypothalamus and plasma of hypertensive rats after sympathetic receptor blockade. 2011 A202 8th IBRO CONGRESS 14-18 July Florence Italy.