Aortic cell apoptosis in rat primary aldosteronism model

  • Yongji Yan (闫永吉)
  • Jinzhi Ouyang (欧阳金芝)
  • Chao Wang (王超)
  • Zhun Wu (吴 准)
  • Xin Ma (马 鑫)
  • Hongzhao Li (李宏召)
  • Hua Xu (徐 华)
  • Zheng Hu (胡 争)
  • Jun Li (李 俊)
  • Baojun Wang (王保军)
  • Taoping Shi (史涛坪)
  • Daojing Gong (龚道静)
  • Dong Ni (倪 栋)
  • Xu Zhang (张 旭)
Article

Summary

This study aimed to determine whether aldosterone could induce vascular cell apoptosis in vivo. Thirty-two male rats were randomly divided into 4 groups: vehicle (control), aldosterone, aldosterone plus eplerenone or hydralazine. They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method. After 8 weeks, plasma aldosterone concentration (PAC) and renin activity (PRA) were determined by radioimmunoassay. Aortic apoptosis was examined by TUNEL assay. The levels of cytochrome c and caspase-3 were determined by Western blotting and the expression of Bax and Bcl-2 was detected by immnuohistochemistry and Western blotting. The results showed that as compared with control group, aldosterone-infused rats exhibited: (1) an increase in SBP; (2) significantly elevated PAC with depressed PRA; (3) elevated aortic vascular cell apoptosis accompanied with higher levels of cytochrome c and activated caspase-3; and (4) significantly up-regulated Bax protein with down-regulated Bcl-2. These effects of aldosterone were significantly inhibited after co-administration with eplerenone but not with hydralazine. It was concluded that aldosterone induced vascular cell apoptosis by its direct effect on the aorta via mineralocorticoid receptors and independently of blood pressure, which may contribute to aldosterone-mediated vascular injury.

Key words

aldosteronism apoptosis mineralocorticoid receptor aorta 

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References

  1. 1.
    Milliez P, Girerd X, Plouin PF, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol, 2005, 45(8):1243–1248CrossRefPubMedGoogle Scholar
  2. 2.
    Amano T, Matsubara T, Izawa H, et al. Impact of plasma aldosterone levels for prediction of in-stent restenosis. Am J Cardiol, 2006,97(6):785–788CrossRefPubMedGoogle Scholar
  3. 3.
    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(14):1309–1321CrossRefPubMedGoogle Scholar
  4. 4.
    Fuller PJ, Young MJ. Mechanisms of mineralocorticoid action. Hypertension, 2005,46(6): 1227–1235CrossRefPubMedGoogle Scholar
  5. 5.
    Hatakeyama H, Miyamori I, Fujita T, et al. Vascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells. J Biol Chem, 1994,269(39):24 316–24 320Google Scholar
  6. 6.
    Funder JW, Pearce PT, Smith R, et al. Vascular type I aldosterone binding sites are physiological mineralocor-ticoid receptors. Endocrinology, 1989,125(4):2224–2226CrossRefPubMedGoogle Scholar
  7. 7.
    Hatakeyama H, Inaba S, Takeda R, et al. 11beta-hydroxysteroid dehydrogenase in human vascular cells. Kidney Int, 2000,57(4):1352–1357CrossRefPubMedGoogle Scholar
  8. 8.
    Callera GE, Touyz RM, Tostes RC,et al. Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src. Hypertension, 2005,45(4):773–779CrossRefPubMedGoogle Scholar
  9. 9.
    Hirono Y, Yoshimoto T, Suzuki N, et al. Angiotensin II receptor type 1-mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-indued hypertension: the possible role of local renin-angiotnsin system. Endocrinology, 2007,148(4): 1688–1696CrossRefPubMedGoogle Scholar
  10. 10.
    Iglarz M, Touyz RM, Viel EC, et al. Involvement of oxidative stress in the profibrotic action of aldosterone. Interaction with the renin-angiotension system. Am J Hypertens, 2004,17(7):597–603PubMedGoogle Scholar
  11. 11.
    Lopez-Candales A, Holmes DR, Liao S, et al. Decreased vascular smooth muscle cell density in medial degeneration of human abdominal aortic aneurysms. Am J Pathol, 1997,150(3):993–1007PubMedGoogle Scholar
  12. 12.
    von der Thusen JH, van Vlijmen BJ, Hoeben RC, et al. Induction of atherosclerotic plaque rupture in apolipoprotein E−/− mice after adenovirus-mediated transfer of p53. Circulation, 2002,105(17):2064–2070CrossRefPubMedGoogle Scholar
  13. 13.
    Korshunov VA, Berk BC. Smooth muscle apoptosis and vascular remodeling. Curr Opin Hematol, 2008, 15(3): 250–254CrossRefPubMedGoogle Scholar
  14. 14.
    Durand E, Scoazec A, Lafont A, et al. In vivo induction of endothelial apoptosis leads to vessel thrombosis and endothelial denudation: a clue to the understanding of the mechanisms of thrombotic plaque erosion. Circulation, 2004,109(21):2503–2506CrossRefPubMedGoogle Scholar
  15. 15.
    Patni H, Mathew JT, Luan L, et al. Aldosterone promotes proximal tubular cell apoptosis: role of oxidative stress. Am J Physiol Renal Physiol, 2007, 293(4): F1065–1071CrossRefPubMedGoogle Scholar
  16. 16.
    Mathew JT, Patni H, Chaudhary AN, et al. Aldosterone induces mesangial cell apoptosis both in vivo and in vitro. Am J Physiol Renal Physiol, 2008,295(1):F73–81CrossRefPubMedGoogle Scholar
  17. 17.
    Hayashi H, Kobara M, Abe M, et al. Aldosterone nongenomically produces NADPH oxidase-dependent reactive oxygen species and induces myocyte apoptosis. Hypertens Res, 2008,31(2):363–375CrossRefPubMedGoogle Scholar
  18. 18.
    Sharifi AM, Schiffrin EL. Apoptosis in aorta of deoxycorticosterone acetate-salt hypertensive rats: effect of endothelin receptor antagonism. J Hypertens, 1997, 15(12 Pt 1):1441–1448CrossRefPubMedGoogle Scholar
  19. 19.
    Wei Y, Whaley-Connell AT, Habibi J, et al. Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury via rescuing protein kinase B activation. Hypertension, 2009,53(2):158–165CrossRefPubMedGoogle Scholar
  20. 20.
    Lumachi F, Ermani M, Basso SM, et al. Long-term results of adrenalectomy in patients with aldosterone-producing adenomas: multivariate analysis of factors affecting unresolved hypertension and review of the literature. Am Surg, 2005,71(10):864–869PubMedGoogle Scholar
  21. 21.
    Struthers A, Krum H, Williams GH. A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin Cardiol, 2008,31(4):153–158CrossRefPubMedGoogle Scholar
  22. 22.
    Williams TA, Verhovez A, Milan A, et al. Protective effect of spironolactone on endothelial cell apoptosis. Endocrinology, 2006,147(5):2496–2505CrossRefPubMedGoogle Scholar
  23. 23.
    Li Y, Song YH, Mohler J, et al. ANG II induces apoptosis of human vascular smooth muscle via extrinsic pathway involving inhibition of Akt phosphorylation and increased FasL expression. Am J Physiol Heart Circ Physiol, 2006,290(5):H2116–2123CrossRefPubMedGoogle Scholar
  24. 24.
    Mercer J, Mahmoudi M, Bennett M. DNA damage, p53, apoptosis and vascular disease. Mutat Res, 2007, 621(1–2):75–86PubMedGoogle Scholar
  25. 25.
    Kutuk O, Basaga H. Bcl-2 protein family: implications in vascular apoptosis and atherosclerosis. Apoptosis, 2006,11(10):1661–1675CrossRefPubMedGoogle Scholar
  26. 26.
    Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell, 1993, 74(4):609–619CrossRefPubMedGoogle Scholar
  27. 27.
    Schnackenberg CG, Welch WJ, Wilcox CS. Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: role of nitric oxide. Hypertension, 1998,32(1):59–64PubMedGoogle Scholar
  28. 28.
    Munzel T, Kurz S, Rajagopalan S, et al. Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug. J Clin Invest, 1996,98(6): 1465–1470CrossRefPubMedGoogle Scholar
  29. 29.
    Sharifi AM, Schiffrin EL. Apoptosis in vasculature of spontaneously hypertensive rats: effect of an angiotensin converting enzyme inhibitor and a calcium channel antagonist. Am J Hypertens, 1998,11(9):1108–1116CrossRefPubMedGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Yongji Yan (闫永吉)
    • 1
    • 2
  • Jinzhi Ouyang (欧阳金芝)
    • 3
  • Chao Wang (王超)
    • 4
  • Zhun Wu (吴 准)
    • 1
  • Xin Ma (马 鑫)
    • 2
  • Hongzhao Li (李宏召)
    • 2
  • Hua Xu (徐 华)
    • 1
  • Zheng Hu (胡 争)
    • 1
  • Jun Li (李 俊)
    • 1
  • Baojun Wang (王保军)
    • 2
  • Taoping Shi (史涛坪)
    • 2
  • Daojing Gong (龚道静)
    • 1
  • Dong Ni (倪 栋)
    • 1
  • Xu Zhang (张 旭)
    • 1
    • 2
  1. 1.Department of Urology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of Urology, Chinese People’s Liberation Army General HospitalMilitary Postgraduate Medical CollegeBeijingChina
  3. 3.Department of Endocrinology, Chinese People’s Liberation Army General HospitalMilitary Postgraduate Medical CollegeBeijingChina
  4. 4.Department of UrologyJining First People’s HospitalJiningChina

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