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The potential role of the angiotensin subtype 2 receptor in cardiovascular protection

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Abstract

Advances in our knowledge of the renin-angiotensin system have led to better understanding of the mechanisms contributing to the development of cardiovascular, renal, and metabolic disorders. Similarly, the discovery of new components of this system offers opportunities to develop new therapeutic tools to manage these diseases. Angiotensin subtype 2 (AT2) receptor represents one of those components with the potential for improving cardiovascular protection. Current knowledge suggests that the AT2 receptor antagonizes the effects of the angiotensin subtype 1 receptor. AT2 receptor activation is linked to vasodilation, nitric oxide production, and antiproliferative and anti-inflammatory effects. The role of the AT2 receptor in inducing natriuresis, inhibiting renin release, limiting atherosclerosis, and promoting remodeling after myocardial infarction is reviewed in this article.

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References and Recommended Reading

  1. Naseem RH, Hedegard W, Henry TD, et al.: Plasma cathepsin D isoforms and their active metabolites increase after myocardial infarction and contribute to plasma renin activity. Basic Res Cardiol 2005, 100:139–146.

    Article  PubMed  CAS  Google Scholar 

  2. Borges JC, Silva JA Jr, Gomes MA, et al.: Tonin in rat heart with experimental hypertrophy. Am J Physiol Heart Circ Physiol 2003, 284:H2263–H2268.

    PubMed  CAS  Google Scholar 

  3. Borland JA, Kelsall C, Yacoub MH, Chester AH: Expression, localization and function of ACE and chymase in normal and atherosclerotic human coronary arteries. Vascul Pharmacol 2005, 42:99–108.

    Article  PubMed  CAS  Google Scholar 

  4. Siragy HM: AT1 and AT2 receptor in the kidney: role in health and disease. Semin Nephrol 2004, 24:93–100.

    Article  PubMed  CAS  Google Scholar 

  5. Nguyen G, Burcklé CA, Sraer JD: Renin/prorenin-receptor biochemistry and functional significance. Curr Hypertens Rep 2004, 6:129–132.

    Article  PubMed  Google Scholar 

  6. Guy JL, Jackson RM, Jensen HA, et al.: Identification of critical active-site residues in angiotensin-converting enzyme-2 (ACE2) by site-directed mutagenesis. FEBS J 2005, 272:3512–3520.

    Article  PubMed  CAS  Google Scholar 

  7. Faria-Silva R, Duarte FV, Santos RA: Short-term angiotensin(1–7) receptor Mas stimulation improves endothelial function in normotensive rats. Hypertension 2005, 46:948–952.

    Article  PubMed  CAS  Google Scholar 

  8. Siragy H, Huang J, Lieb DC: The development of the direct renin inhibitor aliskiren: treating hypertension and beyond. Expert Opin Emerg Drugs 2008, 13:417–430.

    Article  PubMed  CAS  Google Scholar 

  9. Siragy HM, Xue C, Abadir P, Carey RM: Angiotensin subtype-2 receptors inhibit renin biosynthesis and angiotensin II formation. Hypertension 2005, 45:133–137.

    PubMed  CAS  Google Scholar 

  10. Nguyen G, Delarue F, Burcklé C, et al.: Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest 2002, 109:1417–1427.

    PubMed  CAS  Google Scholar 

  11. Siragy HM, Huang J: Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity. Exp Physiol 2008, 93:709–714.

    Article  PubMed  CAS  Google Scholar 

  12. Suzuki F, Hayakawa M, Nagakawa T, et al.: Human prorenin has ‘gate and handle’ regions for its nonproteolytic activation. J Biol Chem 2003, 278:22217–22222.

    Article  PubMed  CAS  Google Scholar 

  13. Burcklé CA, Danser AHJ, Müller DN, et al.: Elevated blood pressure and heart rate in human renin receptor transgenic rats. Hypertension 2006, 47:552–556.

    Article  PubMed  Google Scholar 

  14. Ichihara A, Suzuki F, Nakagawa T, et al.: Prorenin receptor blockade inhibits development of glomerulosclerosis in diabetic angiotensin II type 1a receptor deficient mice. J Am Soc Nephrol 2006, 17:1950–1961.

    Article  PubMed  CAS  Google Scholar 

  15. de Gasparo M, Catt KJ, Inagami T, et al.: International Union of Pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev 2000, 52:415–472.

    PubMed  Google Scholar 

  16. Siragy HM, de Gasparo M, Carey RM: Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats. Hypertension 2000, 35:1074–1077.

    PubMed  CAS  Google Scholar 

  17. Siragy HM, Carey RM: The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest 1997, 100:264–269.

    Article  PubMed  CAS  Google Scholar 

  18. Siragy HM, Carey RM: The subtype-2 (AT2) angiotensin receptor regulates renal cyclic guanosine 3′,5′-monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats. J Clin Invest 1996, 97:1978–1982.

    Article  PubMed  CAS  Google Scholar 

  19. Nouet S, Amzallag N, Li JM, et al.: Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem 2004, 279:28989–28997.

    Article  PubMed  CAS  Google Scholar 

  20. Hannan RE, Davis EA, Widdop RE: Functional role of angiotensin II AT2 receptor in modulation of AT1 receptor-mediated contraction in rat uterine artery: involvement of bradykinin and nitric oxide. Br J Pharmacol 2003, 140:987–995.

    Article  PubMed  CAS  Google Scholar 

  21. Widdop RE, Matrougui K, Levy BI, Henrion D: AT2 receptor-mediated relaxation is preserved after long-term AT1 receptor blockade. Hypertension 2002, 40:516–520.

    Article  PubMed  CAS  Google Scholar 

  22. Ozono R, Wang ZQ, Moore AF, et al.: Expression of the subtype 2 angiotensin (AT2) receptor protein in rat kidney. Hypertension 1997, 30:1238–1246.

    PubMed  CAS  Google Scholar 

  23. Siragy HM, Carey RM: Protective role of the angiotensin AT2 receptor in a renal wrap hypertension model. Hypertension 1999, 33:1237–1243.

    PubMed  CAS  Google Scholar 

  24. Savoia C, Touyz RM, Volpe M, Schiffrin EL: Angiotensin type 2 receptor in resistance arteries of type 2 diabetic hypertensive patients. Hypertension 2007, 49:341–346.

    Article  PubMed  CAS  Google Scholar 

  25. Gilles R, Vingerhoedt N, Howes J, et al.: Increase in systemic blood pressure during intra-arterial PD123319 infusion: evidence for functional expression of angiotensin type 2 receptors in normal volunteers. Blood Press 2004, 13:110–114.

    Article  PubMed  CAS  Google Scholar 

  26. Siragy HM, Inagami T, Carey RM: NO and cGMP mediate angiotensin AT2 receptor-induced renal renin inhibition in young rats. Am J Physiol Regul Integr Comp Physiol 2007, 293:R1461–R1467.

    PubMed  CAS  Google Scholar 

  27. Siragy HM, Inagami T, Ichiki T, Carey RM: Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor. Proc Natl Acad Sci U S A 1999, 96:6506–6510.

    Article  PubMed  CAS  Google Scholar 

  28. Padia SH, Howell NL, Siragy HM, Carey RM: Renal angiotensin type 2 receptors mediate natriuresis via angiotensin III in the angiotensin II type 1 receptor-blocked rat. Hypertension 2006, 47:537–544.

    Article  PubMed  CAS  Google Scholar 

  29. Hakam AC, Hussain T: Angiotensin II AT2 receptors inhibit proximal tubular Na +-K +-ATPase activity via a NO/cGMP-dependent pathway. Am J Physiol Renal Physiol 2006, 290:F1430–F1436.

    Article  PubMed  CAS  Google Scholar 

  30. Hakam AC, Hussain T: Angiotensin II type 2 receptor agonist directly inhibits proximal tubule sodium pump activity in obese but not in lean Zucker rats. Hypertension 2006, 47:1117–1124.

    Article  PubMed  CAS  Google Scholar 

  31. Sales VL, Sukhova GK, Lopez-Ilasaca MA, et al.: Angiotensin type 2 receptor is expressed in murine atherosclerotic lesions and modulates lesion evolution. Circulation 2005, 112:3328–3336.

    Article  PubMed  CAS  Google Scholar 

  32. Dandapat A, Hu CP, Chen J, et al.: Over-expression of angiotensin II type 2 receptor (agtr2) decreases collagen accumulation in atherosclerotic plaque. Biochem Biophys Res Commun 2008, 366:871–877.

    Article  PubMed  CAS  Google Scholar 

  33. Oishi Y, Ozono R, Yoshizumi M, et al.: AT2 receptor mediates the cardioprotective effects of AT1 receptor antagonist in post-myocardial infarction remodeling. Life Sci 2006, 80:82–88.

    Article  PubMed  CAS  Google Scholar 

  34. Jugdutt BI, Menon V: AT2 receptor and apoptosis during AT1 receptor blockade in reperfused myocardial infarction in the rat. Mol Cell Biochem 2004, 262:203–214.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Helmy M. Siragy.

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Siragy, H.M. The potential role of the angiotensin subtype 2 receptor in cardiovascular protection. Current Science Inc 11, 260–262 (2009). https://doi.org/10.1007/s11906-009-0044-3

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