Rac1 GTPase in rodent kidneys is essential for salt-sensitive hypertension via a mineralocorticoid receptor-dependent pathway

Journal of Clinical Investigation

Volumn 121, Issue 8, 2011, Pages 3233-3243

  Shibata, Shigeru ^a   Mu, ShengYu ^a   Kawarazaki, Hiroo ^a   Muraoka, Kazuhiko ^a   Ishizawa, Ken Ichi ^a   Yoshida, Shigetaka ^a   Kawarazaki, Wakako ^a   Takeuchi, Maki ^a   Ayuzawa, Nobuhiro ^a   Miyoshi, Jun ^b   Takai, Yoshimi ^c   Ishikawa, Akira ^a   Shimosawa, Tatsuo ^a   Ando, Katsuyuki ^a   Nagase, Miki ^a   Fujita, Toshiro ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b OSAKA MEDICAL CENTER FOR CANCER AND CARDIOVASCULAR DISEASES   (Japan)

^c KOBE UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; ALDOSTERONE; EPLERENONE; FASUDIL; GUANOSINE TRIPHOSPHATASE; MINERALOCORTICOID RECEPTOR; NEPHRIN; RAC1 PROTEIN; SERUM AND GLUCOCORTICOID REGULATED KINASE 1;

ALBUMINURIA; ALDOSTERONE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD PRESSURE; CONTROLLED STUDY; DOWN REGULATION; ENZYME INHIBITION; GENE EXPRESSION; GLOMERULOSCLEROSIS; HYPERTENSION; KIDNEY; KIDNEY INJURY; NONHUMAN; PRIORITY JOURNAL; RAT; SALT LOADING; UPREGULATION;

ALDOSTERONE; ANIMALS; HYPERTENSION; KIDNEY; KIDNEY DISEASES; MALE; MICE; MICE, TRANSGENIC; MODELS, BIOLOGICAL; PROTEINURIA; RAC1 GTP-BINDING PROTEIN; RATS; RATS, INBRED DAHL; RECEPTORS, MINERALOCORTICOID; SODIUM CHLORIDE, DIETARY;

EID: 79960972766     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI43124     Document Type: Article

References (62)

1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365(9455):217- 223. (Pubitemid 40138015)
2. Fujita T, Henry WL, Bartter FC, Lake CR, Delea CS. Factors influencing blood pressure in salt-sensitive patients with hypertension. Am J Med. 1980;69(3):334-344. (Pubitemid 10059678)
3. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ. 1988;297(6644):319-328.
4. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell. 2001;104(4):545-556. (Pubitemid 32201949)
5. Guyton AC. Blood pressure control - special role of the kidneys and body fluids. Science. 1991;252(5014):1813-1816. (Pubitemid 21917099)
6. He FJ, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev. 2004;(3):CD004937.
7. Tuomilehto J, et al. Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study. Lancet. 2001;357(9259):848-851. (Pubitemid 32239370)
8. Bibbins-Domingo K, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med. 2010;362(7):590-599.
9. Cianciaruso B, et al. Salt intake and renal outcome in patients with progressive renal disease. Miner Electrolyte Metab. 1998;24(4):296-301. (Pubitemid 28108269)
10. Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int. 2003;63(5):1791-1800. (Pubitemid 36513325)
11. Nishiyama A, et al. Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats. Hypertension. 2004;43(4):841-848. (Pubitemid 38405598)
12. Fujita T. Mineralocorticoid receptors, salt-sensitive hypertension, and metabolic syndrome. Hypertension. 2010;55(4):813-818.
13. Rossi GP, Sechi LA, Giacchetti G, Ronconi V, Strazzullo P, Funder JW. Primary aldosteronism: cardiovascular, renal and metabolic implications. Trends Endocrinol Metab. 2008;19(3):88-90. (Pubitemid 351442920)
14. Wang Q, et al. Chronic hyperaldosteronism in a transgenic mouse model fails to induce cardiac remodeling and fibrosis under a normal-salt diet. Am J Physiol Renal Physiol. 2004;286(6):F1178-F1184. (Pubitemid 38656375)
15. Nagase M, Matsui H, Shibata S, Gotoda T, Fujita T. Salt-induced nephropathy in obese spontaneously hypertensive rats via paradoxical activation of the mineralocorticoid receptor: role of oxidative stress. Hypertension. 2007;50(5):877-883. (Pubitemid 350287529)
16. Nagata K, et al. Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and failure in low-aldosterone hypertensive rats. Hypertension. 2006;47(4):656-664. (Pubitemid 43740235)
17. Williams GH, et al. Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol. 2004;93(8):990-996. (Pubitemid 38479452)
18. Funder JW. Is aldosterone bad for the heart? Trends Endocrinol Metab. 2004;15(4):139-142. (Pubitemid 38510491)
19. Shibata S, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med. 2008;14(12):1370-1376.
20. Rapp JP, Dahl LK. Suppression of aldosterone in salt susceptible and salt resistant rats. Endocrinology. 1973;92(4):1286-1289.
21. Wulff P, et al. Impaired renal Na(+) retention in the sgk1-knockout mouse. J Clin Invest. 2002;110(9):1263-1268. (Pubitemid 35285752)
22. Pearce D, Kleyman TR. Salt, sodium channels, and SGK1. J Clin Invest. 2007;117(3):592-595. (Pubitemid 46348515)
23. Zhang W, et al. Aldosterone-induced Sgk1 relieves Dot1a-Af9-mediated transcriptional repression of epithelial Na+ channel alpha. J Clin Invest. 2007;117(3):773-783. (Pubitemid 46348536)
24. Quinkler M, et al. Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation. 2005;112(10):1435-1443. (Pubitemid 41291769)
25. Farjah M, Roxas BP, Geenen DL, Danziger RS. Dietary salt regulates renal SGK1 abundance: relevance to salt sensitivity in the Dahl rat. Hypertension. 2003;41(4):874-878. (Pubitemid 36418459)
26. Aoi W, et al. Abnormal expression of ENaC and SGK1 mRNA induced by dietary sodium in Dahl salt-sensitively hypertensive rats. Cell Biol Int. 2007;31(10):1288-1291. (Pubitemid 47030984)
27. Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49(2):355-364. (Pubitemid 46143013)
28. Terada Y, et al. Aldosterone stimulates proliferation of mesangial cells by activating mitogen-activated protein kinase 1/2, cyclin D1, and cyclin A. J Am Soc Nephrol. 2005;16(8):2296-2305. (Pubitemid 41725047)
29. Raij L, Luscher TF, Vanhoutte PM. High potassium diet augments endothelium-dependent relaxations in the Dahl rat. Hypertension. 1988;12(6):562-567. (Pubitemid 19030501)
30. Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci U S A. 2004;101(20):7618-7623. (Pubitemid 38658078)
31. Cancelas JA, Lee AW, Prabhakar R, Stringer KF, Zheng Y, Williams DA. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med. 2005;11(8):886-891. (Pubitemid 41161122)
32. Nishikimi T, et al. Fasudil, a Rho-kinase inhibitor, attenuates glomerulosclerosis in Dahl salt-sensitive rats. J Hypertens. 2004;22(9):1787-1796. (Pubitemid 39141972)
33. Brilla CG, Weber KT. Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. J Lab Clin Med. 1992;120(6):893-901. (Pubitemid 23002899)
34. Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev. 2001;81(1):153-208. (Pubitemid 32098004)
35. Franceschini N, et al. A quantitative trait loci-specific gene-by-sex interaction on systolic blood pressure among American Indians: the Strong Heart Family Study. Hypertension. 2006;48(2):266-270. (Pubitemid 44309822)
36. Wilk JB, et al. Genome-wide linkage analyses for age at diagnosis of hypertension and early-onset hypertension in the HyperGEN study. Am J Hypertens. 2004;17(9):839-844. (Pubitemid 39201102)
37. Garcia-Mata R, Wennerberg K, Arthur WT, Noren NK, Ellerbroek SM, Burridge K. Analysis of activated GAPs and GEFs in cell lysates. Methods Enzymol. 2006;406:425-437. (Pubitemid 43207456)
38. Simon AR, Vikis HG, Stewart S, Fanburg BL, Cochran BH, Guan KL. Regulation of STAT3 by direct binding to the Rac1 GTPase. Science. 2000; 290(5489):144-147.
39. Deng AY, Dutil J, Sivo Z. Utilization of marker-assisted congenics to map two blood pressure quantitative trait loci in Dahl rats. Mamm Genome. 2001;12(8):612-616. (Pubitemid 32675528)
40. Rapp JP, Garrett MR, Deng AY. Construction of a double congenic strain to prove an epistatic interaction on blood pressure between rat chromosomes 2 and 10. J Clin Invest. 1998;101(8):1591-1595. (Pubitemid 28198487)
41. Sakakibara T, Nemoto Y, Nukiwa T, Takeshima H. Identification and characterization of a novel Rho GTPase activating protein implicated in receptor-mediated endocytosis. FEBS Lett. 2004;566(1-3):294-300. (Pubitemid 38625975)
42. Palijan A, Dutil J, Deng AY. Quantitative trait loci with opposing blood pressure effects demonstrating epistasis on Dahl rat chromosome 3. Physiol Genomics. 2003;15(1):1-8.
43. Seikaly MG, Arant BS Jr, Seney FD Jr. Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest. 1990;86(4):1352-1357. (Pubitemid 20370446)
44. Crowley SD, et al. Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system. J Clin Invest. 2005;115(4):1092-1099. (Pubitemid 40489414)
45. Hall JE, Guyton AC, Trippodo NC, Lohmeier TE, McCaa RE, Cowley AW Jr. Intrarenal control of electrolyte excretion by angiotensin II. Am J Physiol. 1977;232(6):F538-F544.
46. Zhao D, Seth DM, Navar LG. Enhanced distal nephron sodium reabsorption in chronic angiotensin IIinfused mice. Hypertension. 2009;54(1):120-126.
47. Kobori H, Nishiyama A, Abe Y, Navar LG. Enhancement of intrarenal angiotensinogen in Dahl salt-sensitive rats on high salt diet. Hypertension. 2003;41(3):592-597. (Pubitemid 36314637)
48. Jaffe IZ, Mendelsohn ME. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res. 2005;96(6):643-650. (Pubitemid 40478331)
49. Servitja JM, Marinissen MJ, Sodhi A, Bustelo XR, Gutkind JS. Rac1 function is required for Src-induced transformation. Evidence of a role for Tiam1 and Vav2 in Rac activation by Src. J Biol Chem. 2003;278(36):34339-34346. (Pubitemid 37553278)
50. Tsai CT, et al. Angiotensin II activates signal transducer and activators of transcription 3 via Rac1 in atrial myocytes and fibroblasts: implication for the therapeutic effect of statin in atrial structural remodeling. Circulation. 2008;117(3):344-355.
51. Takeda Y, Yoneda T, Demura M, Furukawa K, Miyamori I, Mabuchi H. Effects of high sodium intake on cardiovascular aldosterone synthesis in stroke-prone spontaneously hypertensive rats. J Hypertens. 2001;19(3 pt 2):635-639. (Pubitemid 32280957)
52. Rossier MF, Lenglet S, Vetterli L, Python M, Maturana A. Corticosteroids and redox potential modulate spontaneous contractions in isolated rat ventricular cardiomyocytes. Hypertension. 2008;52(4):721-728.
53. Mihailidou AS, Loan Le TY, Mardini M, Funder JW. Glucocorticoids activate cardiac mineralocorticoid receptors during experimental myocardial infarction. Hypertension. 2009;54(6):1306-1312.
54. Funder JW. Minireview: Aldosterone and mineralocorticoid receptors: past, present, and future. Endocrinology. 2010;151(11):5098-5102.
55. Krug AW, et al. Elevated mineralocorticoid receptor activity in aged rat vascular smooth muscle cells promotes a proinflammatory phenotype via extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and epidermal growth factor receptor-dependent pathways. Hypertension. 2010;55(6):1476-1483.
56. Yokota K, et al. Coactivation of the N-terminal transactivation of mineralocorticoid receptor by Ubc9. J Biol Chem. 2007;282(3):1998-2010. (Pubitemid 47076701)
57. Massaad C, Houard N, Lombes M, Barouki R. Modulation of human mineralocorticoid receptor function by protein kinase A. Mol Endocrinol. 1999;13(1):57-65. (Pubitemid 29022279)
58. Kurtz TW, Griffin KA, Bidani AK, Davisson RL, Hall JE. Recommendations for blood pressure measurement in humans and experimental animals. Part 2: Blood pressure measurement in experimental animals: a statement for professionals from the subcommittee of professional and public education of the American Heart Association council on high blood pressure research. Hypertension. 2005;45(2):299-310. (Pubitemid 40179976)
59. Higashi M, et al. Long-term inhibition of Rhokinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo: effect on endothelial NAD(P)H oxidase system. Circ Res. 2003;93(8):767-775. (Pubitemid 37288672)
60. Togawa A, et al. Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDI-alpha. Oncogene. 1999;18(39):5373-5380. (Pubitemid 29469225)
61. Shibata S, Nagase M, Fujita T. Fluvastatin ameliorates podocyte injury in proteinuric rats via modulation of excessive Rho signaling. J Am Soc Nephrol. 2006;17(3):754-764.
62. Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T, Fujita T. Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. Hypertension. 2006;47(6):1084-1093. (Pubitemid 44289165)