Renin-angiotensin-aldosteron system: evolution of views from renin discovery to nowadays. Perspectives of therapeutic block


Cite item

Full Text

Abstract

Recent revolution in the knowledge about structure, physiological and pathophysiological effects of renin-angiotensin-aldosteron system (RAAS) took place recently when it was discovered that local synthesis of all the RAAS components occurs in target organs and their tissues (the heart, kidneys, vessels, brain tissues). It was found that besides classic RAAS acting via activation of angiotensin II (Ang-II) and its receptors, there is an alternative RAAS opposed to atherogenic potential of Ang-II. Renin and prorenin are shown to have both enzymatic and hormonal activities. Wider understanding appeared of extrarenal effects of aldosteron, its non-genomic activity. The above discoveries open new opportunities for pharmacological regulation of RAAS activity, which enables more effectively correct overactivity of this system in organs at risk of negativeAng-II impact.

About the authors

Marina Vladimirovna Shestakova

Email: nephro@endocrincentr.ru

M V Shestakova

Endocrinological Research Center, Moscow

Endocrinological Research Center, Moscow

References

  1. Phillips M. I., Schmidt-Ott K. M. The discovery of renin 100 years ago. News Physiol. Sci. 1999; 14: 271-274.
  2. Cook W. F., Pickering G. W. The location of renin in the rabbit kidney. J. Physiol. (Lond.). 1959; 149: 526-536.
  3. Urata H., Kinoshita A., Misono K. S. et al. Identification of a high specific chymase as a major angiotensin II-forming enzyme in the human heart. J. Biol. Chem. 1990; 265: 22348- 22357.
  4. Okunishi H., Miyazaki M., Okamura T. et al. Different distribution of two types of angiotensin II-generating enzymes in the aortic wall. Biochem. Biophys. Res. Commun. 1987; 149: 1186-1192.
  5. Bottary S. P., de Gasparo M., Steckeling U. M. et al. Angiotensin II receptor subtypes: characterization, signaling mechanisms, and possible physiologic implications. Front. Neuroendocrinol. 1993; 14: 123-171.
  6. Reaux A., Fournie-Zaluski M. C., Llorens-Cortes C. Angiotensin III: a central regulator of vasopressin release and blood pressure. Trends Endocrinol. Metab. 2001; 12: 157-162.
  7. Mustafa T., Lee J. H., Chai S. Y. et al. Bioactive angiotensin peptides: focus on angiotensin IV. JRAAS 2001; 2: 205-210.
  8. Tipnis S. R., Hooper N. M., Hyde R. et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem. 2000; 275: 3338-3343.
  9. Santos R. A., Ferreira A. J. Angiotensin-(1-7) and the renin- angiotensin system. Curr. Opin. Nephrol. Hypertens. 2007; 16: 122-128.
  10. Nguyen G., Delarue F., Burckle C. et al. Pivotal role of the renin/prorenin receptors in angiotensin II production and cellular responses to renin. J. Clin. Invest. 2002; 109: 1417-1427.
  11. Nguyen G., Danser A. H. Prorenin and (pro)renin receptor: a review of available data from in vitro studies and experimental models in rodents. Exp. Physiol. 2009; 93: 557-563.
  12. Deinum J., Ronn B., Mathiesen E. et al. Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus. Diabetologia 1999; 42: 1006-1010.
  13. Danser A. H., van den Dorpel M. A., Deinum J. et al. Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy. J. Clin. Endocrinol. 1989; 68: 160-167.
  14. Mulrow P. J., Ganong W. F. Stimulation of aldosterone secretion by angiotensin II. Yale J. Biol. Med. 1961; 33: 386-395.
  15. Hatakeyama H., Miyamori I., Fujita T. et al. Vascular aldosterone. Biosynthesis and a link to angiotensin II induced hypertrophy of vascular smooth cells. J. Biol. Chem. 1994; 269: 24316-24320.
  16. Bonvalet J. P., Alfaidy N., Farman N. et al. Aldosterone: intracellular receptors in human heart. Eur. Heart J. 1995; 16 (Suppl. N): 92-97.
  17. MacKenzie S. M., Clark C. J., Fraser R. et al. Expression of 11β-hydroxylase and aldosterone synthase genes in the rat brain. J. Mol. Endocrinol. 2000; 24: 321-328.
  18. Satoh M., Nakamura M., Saitoh H. et al. Aldosterone sunthase (CYP11B2) expression and myocardial fibrosis in the failing human heart. Clin. Sci. 2002; 102: 381-386.
  19. Schlaich M. P., Schobel H. P., Hilgers K. et al. Impact of aldosterone on left-ventricular structure and function in young normotensive and mildly hypertensive subjects. Am. J. Cardiol. 2000; 85: 1199-1206.
  20. Duprez D., De Buyzere M., Reitzschel E. R. et al. Aldosterone and vascular damage. Curr. Hypertens. Rep. 2000; 2: 327- 334.
  21. Remuzzi G., Cattaneo D., Perico N. The aggravating mechanisms of aldosterone on kidney fibrosis. J. Am. Soc. Nephrol. 2008; 19: 1459-1462.
  22. Pimenta E., Calhoun D. A. Aldosterone, dietary salt, and kidney disease. Hypertension 2006; 48: 209-210.
  23. Tae-Yon Chun, Pratt J. H. Non-genomic effects of aldosterone: new actions and questions. Trends Endocrinol. Metab. 2004; 15: 353-354.
  24. Struthers A. D., MacDonald T. M. Review of aldosterone- and angiotensin II-induced target organ damage and prevention. Cardiovasc. Res. 2004; 61: 663-670.
  25. Pitt B., Zannad F., Remme W. J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N. Engl. J. Med. 1999; 341: 709-717.
  26. Pitt B., Remme W., Zannad F. et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 2003; 348: 1309-1321.
  27. Pitt B., Reichek N., Metscher R. et al. Efficacy and safety of eplerenon, enalapril, and eplerenon/enalapril combination therapy in patients with left ventricular hypertrophy. Am. J. Hypertens. 2002; 15: 24A.
  28. Epstein M., Buckalew V., Martinez F. et al. Antiproteinuric efficacy of eplerenon, enalapril, and eplerenon/enalapril combination in diabetic hypertensives with microalbuminuria. Am. J. Hypertens. 2002; 15: 25A.
  29. Anderson S. Role of local and systemic angiotensin in diabetic renal disease. Kidney Int. 1997; 62 (Suppl. 63): 107-110.
  30. Шамхалова М. Ш., Трубицына Н. П., Шестакова М. В. Феномен частичного ускользания блокады ангиотензина II у больных сахарным диабетом типа 2 и диабетической нефропатией. Тер. арх. 2008; 1: 49-52.
  31. Roig E., Perez-Villa F., Morales M. et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur. Heart J. 2000; 21: 53-57.
  32. Sanoski C. A., Pharm D. Aliskiren: an oral renin inhibitor for the treatment of hypertension. Pharmacotherapy 2009; 29: 193-212.
  33. Parving H. H., Persson F., Lewis J. B. et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N. Engl. J. Med. 2008; 358: 2433-2446.
  34. Reudelhuber T. L. Prorenin, renin, and their receptor, moving targets. Hypertension 2010; 55: 1071-1074.
  35. Steckelings U. M., Rompe F., Kaschina E. et al. The past, present and future of AT2-receptor stimulation. JRAAS 2010; 11: 67-73.
  36. Santos R. A., Ferreira A. J. Pharmacological effects of AVE 0991, a nonpeptide angiotensin-(1-7) receptor agonist. Cardiovasc. Drug Rev. 2006; 24: 239-246.
  37. Lea W. B., Kwak E. S., Luther J. M. et al. Aldosterone antagonism or synthase inhibition reduces end-organ damage induces by treatment with angiotensin and high salt. Kidney Int. 2009; 75: 936-944.

Copyright (c) 2011 Shestakova M.V., Shestakova M.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies