Journal of the American Society of Hypertension
Volume 2, Issue 6 , Pages 418-424 , November 2008

Ablation of angiotensin (1-7) receptor Mas in C57Bl/6 mice causes endothelial dysfunction

  • Luiza A. Rabelo, PhD

      Affiliations

    • Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
    • Laboratório de Reatividade Cardiovascular, Setor de Fisiologia, Instituto de Ciências Biológicas e da Saúde (ICBS), Universidade Federal de Alagoas, Maceió, Alagoas, Brazil
    • ,
  • Ping Xu

      Affiliations

    • Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
    • ,
  • Mihail Todiras, MD

      Affiliations

    • Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
    • ,
  • Walkyria O. Sampaio

      Affiliations

    • Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
    • ,
  • Jens Buttgereit, PhD

      Affiliations

    • Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
    • ,
  • Michael Bader, PhD

      Affiliations

    • Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
    • ,
  • Robson A.S. Santos, PhD

      Affiliations

    • Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
    • ,
  • Natalia Alenina, PhD

      Affiliations

    • Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
    • Corresponding Author InformationCorresponding author: Natalia Alenina, PhD, Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, D-13125 Berlin-Buch, Germany. Tel: +49 30 9406 3576; fax: +49 30 9406 2110

Received 2 March 2008 ,Accepted 7 May 2008.

References 

  1. Jackson TR, Blair LA, Marshall J, Goedert M, Hanley MR. The Mas oncogene encodes an angiotensin receptor. Nature. 1988;335:437–440
  2. Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, et al. 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
  3. Benter IF, Yousif MH, Anim JT, Cojocel C, Diz DI. Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. Am J Physiol. 2006;290:H684–H691
  4. Grobe JL, Mecca AP, Lingis M, Shenoy V, Bolton TA, Machado JM, et al. Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7). Am J Physiol. 2007;292:H736–H742
  5. Iwata M, Cowling RT, Gurantz D, Moore C, Zhang S, Yuan JX, et al. Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects. Am J Physiol. 2005;289:H2356–H2363
  6. Iyer SN, Ferrario CM, Chappell MC. Angiotensin-(1-7) contributes to the antihypertensive effects of blockade of the renin-angiotensin system. Hypertension. 1998;31:356–361
  7. Santos RA, Ferreira AJ, Nadu AP, Braga AN, de Almeida AP, Campagnole-Santos MJ, et al. Expression of an angiotensin-(1-7)-producing fusion protein produces cardioprotective effects in rats. Physiol Genom. 2004;17:292–299
  8. Kostenis E, Milligan G, Christopoulos A, Sanchez-Ferrer CF, Heringer-Walther S, Sexton PM, et al. G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor. Circulation. 2005;111:1806–1813
  9. Heitsch H, Brovkovych S, Malinski T, Wiemer G. Angiotensin-(1-7)-stimulated nitric oxide and superoxide release from endothelial cells. Hypertension. 2001;37:72–76
  10. Alenina N, Xu P, Rentzsch B, Patkin EL, Bader M. Genetically altered animal models for Mas and angiotensin-(1-7). Exp Physiol. 2008;93:528–537
  11. da Costa Goncalves AC, Leite R, Fraga-Silva RA, Pinheiro SV, Reis AB, Reis FM, et al. Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function. Am J Physiol. 2007;293:H2588–H2596
  12. Sampaio WO, Souza dos Santos RA, Faria-Silva R, da Mata Machado LT, Schiffrin EL, Touyz RM. Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways. Hypertension. 2007;49:185–192
  13. Kumar M, Grammas P, Giacomelli F, Wiener J. Selective expression of c-Mas proto-oncogene in rat cerebral endothelial cells. Neuroreport. 1996;8:93–96
  14. Xu P, Costa-Goncalves AC, Todiras M, Rabelo LA, Sampaio WO, Moura MM, et al. Endothelial dysfunction and elevated blood pressure in Mas gene-deleted mice. Hypertension. 2008;51:574–580
  15. Hartner A, Cordasic N, Klanke B, Veelken R, Hilgers KF. Strain differences in the development of hypertension and glomerular lesions induced by deoxycorticosterone acetate salt in mice. Nephrol Dial Transplant. 2003;18:1999–2004
  16. Pillebout E, Burtin M, Yuan HT, Briand P, Woolf AS, Friedlander G, et al. Proliferation and remodeling of the peritubular microcirculation after nephron reduction: association with the progression of renal lesions. Am J Pathol. 2001;159:547–560
  17. Xu P, Santos RA, Bader M, Alenina N. Alterations in gene expression in the testis of angiotensin-(1-7)-receptor Mas-deficient mice. Regul Pept. 2007;138:51–55
  18. Bohlender J, Menard J, Wagner J, Luft FC, Ganten D. Human renin-dependent hypertension in rats transgenic for human angiotensinogen. Hypertension. 1996;27:535–540
  19. Bohlender J, Menard J, Edling O, Ganten D, Luft FC. Mouse and rat plasma renin concentration and gene expression in (mRen2)27 transgenic rats. Am J Physiol. 1998;274:H1450–H1456
  20. Langenickel TH, Pagel I, Buttgereit J, Tenner K, Lindner M, Dietz R, et al. Rat corin gene: molecular cloning and reduced expression in experimental heart failure. Am J Physiol. 2004;287:H1516–H1521
  21. Gerzer R, Bohme E, Hofmann F, Schultz G. Soluble guanylate cyclase purified from bovine lung contains heme and copper. FEBS Lett. 1981;132:71–74
  22. Walther T, Balschun D, Voigt JP, Fink H, Zuschratter W, Birchmeier C, et al. Sustained long term potentiation and anxiety in mice lacking the Mas protooncogene. J Biol Chem. 1998;273:11867–11873
  23. Wu L, Iwai M, Nakagami H, Chen R, Suzuki J, Akishita M, et al. Effect of angiotensin II type 1 receptor blockade on cardiac remodeling in angiotensin II type 2 receptor null mice. Arterioscler Thromb Vasc Biol. 2002;22:49–54
  24. Gurley SB, Allred A, Le TH, Griffiths R, Mao L, Philip N, et al. Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest. 2006;116:2218–2225
  25. Bendall JK, Heymes C, Wright TJ, Wheatcroft S, Grieve DJ, Shah AM, et al. Strain-dependent variation in vascular responses to nitric oxide in the isolated murine heart. J Mol Cell Cardiol. 2002;34:1325–1333
  26. Lum C, Shesely EG, Potter DL, Beierwaltes WH. Cardiovascular and renal phenotype in mice with one or two renin genes. Hypertension. 2004;43:79–86
  27. Muller DN, Schmidt C, Barbosa-Sicard E, Wellner M, Gross V, Hercule H, et al. Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific expression, and role in renal 20-hydroxyeicosatetraenoic acid formation. Biochem J. 2007;403:109–118
  28. Peiro C, Vallejo S, Gembardt F, Azcutia V, Heringer-Walther S, Rodriguez-Manas L, et al. Endothelial dysfunction through genetic deletion or inhibition of the G protein-coupled receptor Mas: a new target to improve endothelial function. J Hypertens. 2007;25:2421–2425
  29. Lykkesfeldt J. Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clin Chim Acta. 2007;380:50–58
  30. Meagher EA, FitzGerald GA. Indices of lipid peroxidation in vivo: strengths and limitations. Free Radic Biol Med. 2000;28:1745–1750
  31. 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

 This study was supported by Fapemig/CNPq-Pronex (RASS) and DAAD/CAPES (PROBRAL). Part of the Proceedings of the Vasoactive Peptide Symposium, VII International Vasoactive Peptide Symposium in Ouro Preto, February 14–16, 2008.

 Conflict of interest: none.

PII: S1933-1711(08)00092-2

doi: 10.1016/j.jash.2008.05.003

Journal of the American Society of Hypertension
Volume 2, Issue 6 , Pages 418-424 , November 2008

Article Tools

* Image Usage & Resolution