• No results found

Tre kontrollsentraler blir én

4.3 Respondentenes synspunkter

4.3.3 Tre kontrollsentraler blir én

do rato DM (12 meses de DM); D) glomérulo de rato tratado com

losartan (60 dias pós-tratamento). Tecido renal em parafina. Aumento de

200X.

Tabela 1: Peso corpóreo

ZERO 2 meses 4 meses 6 meses 8 meses 10 meses 12 meses CN (n=12) 232 ± 3 339 ± 9 394 ± 6 404 ± 6 415 ± 10 417 ± 10 419 ± 10 DMPRE (n=10) 234 ± 4 289 ± 9 a 311 ± 6 a 326 ± 7 a 341 ± 7 a 345 ± 8 a DM (n=8) 236 ± 3 293 ± 8 a 316 ± 8 a 327 ± 7 a 342 ± 8 a 347 ± 8 a 350 ± 9 a DML50 (n=11) 241 ± 6 300 ± 6 a 319 ± 6 a 332 ± 5 a 341 ± 4 a 346 ± 5 a 345 ± 8 a DML500 (n=12) 241 ± 3 305 ± 5 a 324 ± 5 a 335 ± 6 a 346 ± 3 a 357 ± 3 a 354 ± 10 a a p < 0,05 vs. CN. Valores expressos em gramas.

Tabela 2: Glicemia

ZERO 2 meses 4 meses 6 meses 8 meses 10 meses 12 meses CN (n=12) 80 ± 6 90 ± 8 94 ± 2 86 ± 8 92 ± 4 80 ± 2 90 ± 7 DMPRE (n=10) 390 ± 16 a 420 ± 18 a 415 ± 18 a 326 ± 20 a 405 ± 16 a 360 ± 18 a DM (n=8) 360 ± 12 a 420 ± 20 a 400 ± 15 a 370 ± 15 a 360 ± 18 a 410 ± 16 a 430 ± 16 a DML50 (n=11) 370 ± 15 a 350 ± 16 a 410 ± 19 a 448 ± 14 a 370 ± 20 a 410 ± 15 a 396 ± 18 a DML500 (n=12) 410 ± 18 a 305 ± 15 a 390 ± 16 a 390 ± 12 a 420 ± 17 a 408 ± 19 a 390 ± 15 a Valores expressos em mg/dl. a p < 0,05 vs. CN. 54

Tabela 3: Pressão sistólica

2 meses 10 meses 11 meses 12 meses

CN (n=12) 130 ± 1 135 ± 2 135 ± 5 140 ± 1 DMPRE (n=10) 130 ± 2 135 ± 2 ― ― DM (n=8) 135 ± 1 130 ± 2 135 ± 1 140 ± 3 DML50 (n=11) 130 ± 2 135 ± 1 130 ± 2 120 ± 4 a,b DML500 (n=12) 130 ± 2 135 ± 2 125 ± 2 115 ± 4 a,b Valores expressos em mmHg. a p < 0,05 vs CN; b p< 0,05 vs DM 55

Tabela 4: Albuminúria

2 meses 4 meses 6 meses 8 meses 10 meses 11meses 12 meses CN (n=12) 4 ± 1 5 ± 1 8 ± 1 16 ± 2 24 ± 3 30 ± 5 35 ± 3 DMPRE (n=10) 9 ± 2 16 ± 3 a 32 ± 4 a 65 ± 11 a 112 ± 15 a

DM (n=8) 11 ± 2 18 ± 3 a 34 ± 3 a 54 ± 8 a 114 ± 20 a 120 ± 20 a 131 ± 22 a

DML50 (n=11) 12 ± 1 22 ± 3 a 36 ± 9 a 63 ± 8 a 114 ± 15 a 64 ± 20 a 40 ± 10 b,c

DML500 (n=12) 10 ± 1 18 ± 4 a 33 ± 4 a 76 ± 10 a 113 ± 18 a 46 ± 12 b,c 35 ± 10 b,c

Valores expressos em mg/dia. a p < 0,05 vs CN; b p < 0,05 vs DMPRE; p< 0,05 vs DM. c

Tabela 5: Índice de expansão mesangial, porcentagem de esclerose glomerular, índice de esclerose glomerular, porcentagem de Interstício, infiltração de macrófagos e expressão de vimentina glomerular ao final do período de observação (10 meses após indução de DM para o grupo DMPRE e 12 meses após indução de DM para os demais grupos).

IEM %EG IEG INT (%) Vim (%)

céls/mm2

CN (n=12) 3 ± 1 2 ± 0,3 8 ± 1 1 ± 0,1 25 ± 3 20 ± 1 DMPRE (n=10) 31 ± 6 a 6 ± 1,0 a 24 ± 3 a 1 ± 0,1 24 ± 5 11 ± 1 a

DM (n=8) 141 ± 40 a,b 19 ± 3,0 a,b 50 ± 7 a,b 2 ± 1,0 100 ± 12 a,b 11 ± 1 a

DML50 (n=11) 7 ± 3 b,c 5 ± 2,0 c 11 ± 1 b,c 1 ± 0,3 35 ± 9 c 18 ± 1 b,c

DML500 (n=12) 8 ± 3 b,c 6 ± 1,0 c 14 ± 2 b,c 1 ± 0,2 29 ± 5 c 16 ± 1 b,c

Os valores são expressos em média ± erro padrão. IEM, índice de expansão mesangial; %EG, porcentagem de esclerose glomerular; IEG, índice de esclerose glomerular, INT, área fracional do interstício; Mφ, intensidade de infiltração macrofágica; Vim, expressão glomerular de vimentina. a p < 0,05 vs grupo CN; b p < 0,05 vs grupo DMPRE;

c

p < 0,05 vs grupo DM.

Tabela 6: Creatinina, potássio e aldosterona ao final do período de observação (10 meses após indução de DM para o grupo DMPRE e 12 meses após indução de DM para os demais grupos).

Creatinina Potássio Aldosterona

(mg/dl) (meq/l) (pg/dl) CN (n=12) 1,0 ± 0,1 5,0 ± 0,1 488 ± 75 DMPRE (n=10) 0,8 ± 0,1 5,0 ± 0,2 659 ± 120 DM (n=8) 1,0 ± 0,1 5,5 ± 0,2 971 ± 141 a DML50 (n=11) 1,0 ± 0,1 5,5 ± 0,2 507 ± 81 b DML500 (n=12) 0,8 ± 0,1 5,5 ± 0,1 524 ± 84 b a b p < 0,05 vs DM. p < 0,05 vs CN; 58

REFERÊNCIAS

ADAMCZAK M, GROSS ML, KRTIL J, KOCH A, TYRALLA K, AMANN K, RITZ E. Reversal of glomerulosclerosis after high-dose enalapril treatment in subtotally nephrectomized rats. J. Am. Soc. Nephrol. 2003;14:2833-42.

ANDERSON S, MEYER TW, RENNKE HG, BRENNER BM. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J. Clin. Invest. 1985;76:612-9.

ANDERSON S, RENNKE HG, BRENNER BM. Nifedipinie versus fosinopril in uninephrectomized diabetic rats. Kidney Int. 1992;41:891-7.

ARANDA P, SEGURA J, RUILOPE LM, ARANDA FJ, FRUTAS MA, LÓPEZ V, LOPEZ DE NOVALES E. Long-term renoprotective effects of standard versus high doses of telmisartan in hypertensive nondiabetic nephropathies.

Am. J. Kidney Dis. 2005;46:1074-79.

BALLERMANN BJ, SKOREEKI KL, BRENNER BM. Reduced glomerular angiotensin II receptor density in early untreated diabetes mellitus in the rat.

BATISTA PB, LOPES AA, COSTA FA. Association between attributed cause of end-stage renal disease and risk of death in Brazilian patients receiving renal replacement therapy. Ren Fail. 2005;27:651-6.

BOFFA JJ, LU Y, PLACIER S, STEFANSKI A, DUSSAULE JC, CHATZIANTONIOU C. Regression of renal vascular and glomerular fibrosis: Role of angiotensin II receptor antagonism and matrix metalloproteinases. J. Am. Soc. Nephrol. 2003;14:1132-44.

BORDER WA, NOBLE NA. Interactions of transforming growth factor-beta and angiontensin II in renal fibrosis. Hypertension 1998;31:181-8.

BRENNER BM, COOPER ME, DE ZEEUW D, KEANE WF, MITCH WE, PARVING HH, REMUZZI G, SNAPINN SM, ZHANG Z, SHAHINFAR S. RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N. Engl. J. Med.

2001;345:861-9

BROWNLEE M, CERAMI A, VLASSARA H. Advanced glycosilation end products in tissue and the biochemical basis of diabetic complication. N. Engl. J. Med. 1988;318:1315-21.

BURNS KD. Angiotensin II and its receptor in diabetic kidney. Am. J. Kidney Dis. 2000;36:449-67.

CHENG HF, BURNS KV, HARRIS RC. Reduced proximal tubule angiotensin II receptor expression in streptozotocin induced diabetes mellitus. Kidney Int.

1994;46:1603-10.

CRUZADO JM, LLOBERAS N, TORRAS J, RIERA M, FILLAT C, HERRERO-FRESNEDA I, ARAN JM, ALPEROVICH G, VIDAL A, GRINYO JM. Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats. Diabetes 2004;53:1119-27.

DCCT – THE DIABETES CONTROL AND COMPLICATION TRIAL. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N. Engl. J. Med. 2000;342:381-9.

DEL PRETE D, ANGLANI F, FORINO M, CEOL M, FIORETTO P, NOSADINI R, BAGGIO B, GAMBARO G. Down-regulation of glomerular matrix metalloproteinase-2 gene in human NIDDM. Diabetologia

1997;40:1449-54.

DI PAOLO S, GESUALDO L, RANIERI E, GRANDALIANO G, SCHENA FP. High glucose concentration induces the overexpression of transforming growth factor beta through the activation of a platelet-derived growth factor loop in human mesangial cells. Am. J. Pathol. 1996;149:2095-106.

ESSAWY M, SOYLEMEZOGLU O, MUCHANETA-KUBARA EC, SHORTLAND J, BROWN CB AND EL NAHAS AM. Myofibroblasts and the progression of diabetic nephropathy. Nephrol. Dial. Transplant.

1997;12:43-50.

FIORETTO P, STEFFES MW, SUTHERLAND DE, MAUER M. Sequential renal biopsies in insulin-dependent diabetic patients: structural factors associated with clinical progression. Kidney Int. 1995;48:1929-35.

FIORETTO P, STEFFES MW, SUTHERLAND DE, GOETZ FC, MAUER M. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N. Engl. J. Med. 1998;339:69-75.

FORBES JM, HEWITSON TD, BECKER GJ, JONES CL. Ischemic acute renal failure: long-term histology of cell and matrix changes in the rat. Kidney Int. 2000;57:2375-85.

FRANKEN AA, DERKX FH, MAN INT VELD AJ, HOP WC, VAN RENS GH, PEPERKAMP E , DE JONG PT, SCHALEKAMP MA. High plasma prorenin in diabetes mellitus and its correlation with some complications. J. Clin. Endocrinol. Metab. 1990;71:1008-15.

FUJIHARA CK, PADILHA RM, ZATZ R. Glomerular abnormalities in long- term experimental diabetes: Role of hemodynamic factors and effects of antihypertensive therapy. Diabetes 1992;41:286-93.

FUJIHARA CK, MALHEIROS DMAC, NORONHA IL, DE NUCCI G, ZATZ R. Mycophenolate mofetil reduces renal injury in the chronic nitric oxide synthase inhibition model. Hypertension 2001;37:170-5.

FUJIHARA CK, VELHO M, MALHEIROS DMAC, ZATZ R. An extremely high dose of losartan affords superior renoprotection in the remnant model.

Kidney Int. 2005;67:1913-24.

FURUTA T, SAITO T, OOTAKA T, SOMA J, OBARA K, ABE K, YOSHINAGA, K. The role of macrophages in diabetic glomerulosclerosis.

Am. J. Kidney. Dis. 1993;21:480-5.

GAO X, MAE H, AYABE N, TAKAI T, OSHIMA K, HATTORI M, UEKI T, FUJIMOTO J, TANIZAWA T. Hepatocyte growth factor gene therapy retards the progression of chronic obstructive nephropathy. Kidney Int.

2002;62:1238-48.

GONÇALVES AR, FUJIHARA CK, MATTAR AL, MALHEIROS DM, NORONHA I DE L, DE NUCCI G, ZATZ R. Renal expression of COX-2, ANG II, and AT1 receptor in remnant kidney: Strong renoprotection by therapy with

losartan and a nonsteroidal anti-inflammatory. Am. J. Physiol. Renal Physiol.

2004;286:F945-54.

GREENE EL, KREN S, HOSTETTER TH. Role of aldosterona in remnant kidney model in the rat. J. Clin. Invest. 1996;98:1063-8.

GUPTA S, VERFAILLIE C, CHMIELEWSKI D, KIM Y, ROSEMBERG ME. A role for extrarenal cells in the regeneration following acute renal failure.

Kidney Int. 2002;62:1285-90.

HAN SY, JEE YH, HAN HK, KANG YS, KIM HK, HAN JY, KIM YS, CHA DR. An imbalance between matrix-metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 contributes to the development of early diabetic nephropathy. Nephrol. Dial. Transplant. 2006;21:2406-16.

HOSTETTER TH, TROY JL, BRENNER BM. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981;19:410-15.

IGLESIAS-DE LA CRUZ MC, ZIYADEH FN, ISONO M, KOUAHOU M, HAN DC, KALLURI R, MUNDEL P, CHEN S. Effects of high glucose and TGF-β1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes. Kidney Int. 2002;62:901-13.

KALE S, KARIHALLOO A, CLARK PR, KASHGARIAN M, KRAUSE DS, CANTLEY LG. Bone marrow stem cells contribute to the regeneration of renal tubules after renal ischemia-reperfusion injury in mice. J. Clin. Invest.

2003;112:42-9.

KLIEM V, JOHNSON RJ, ALPERS CE, YOSHIMURA A, COUSER WG, KOCH KM, FLOEGE J. Mechanisms involved in the pathogenesis of tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int.

1996;49:666-78.

KOMERS R, ALLEN TJ, COOPER ME. Role of endothelium-derived nitric oxide in the pathogenesis of the renal hemodynamic changes of experimental diabetes. Diabetes 1994;43:1190-7.

KRIZ W, GRETZ N, LEMLEY KV. Progression of glomerular diseases: Is the podocyte the culprit ? Kidney Int. 1998;54:687-97.

KRIZ W. The pathogenesis of classical focal glomerulosclerosis. Nephrol. Dial. Transplant. 2003;18:vi39-44.

LEWIS EJ, HUNSICKER LG, BAIN RP, ROHDE RK. Collaborative Study Group. The effect of angiotensin-converting enzime on diabetic nephropathy.

LEWIS EJ, HUNSICKER LG, CLARKE WR, BERL T, POHL MA, LEWIS JB, RITZ E, ATKINS RC, ROHDE R, RAZ I. Collaborative Study Group. Renoprotective effect of the angiotensin receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N. Engl. J. Med.

2001;345:851-60.

MA LJ, NAKAMURA S, ALDIGIER JC, ROSSINI M, YANG H, LIANG X, NAKAMURA I, MARCANTONI C, FOGO AB. Regression of glomerulosclerosis with high-dose angiotensin inhibition is linked to decreased plasminogen activator inhibitor-1. J. Am. Soc. Nephrol.

2005;16:966-76.

MANCINI GAO, CARBONARO JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 1965;2:235-54.

MCLENNAN SV, KELLY DJ, COX AJ, CAO Z, LYONS JG, YUE DK, GILBERT RE. Decreased matrix degradation in diabetic nephropathy. Effects of ACE inhibition on the expression and activities of matrix metalloproteinases. Diabetologia 2002;45:268-75.

MIZUNO S, KUROSAWA T, MATSUMOTO K, MIZUNO-HORIKAWA Y, OKAMOTO M, NAKAMURA T. Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model of chronic renal disease. J. Clin. Invest. 1998;101:1827-34.

MOGENSEN CE. Glomerular filtration rate and renal plasma flow in long- term juvenile diabetics without proteinuria. Br. Med. J. 1972;2:257-9.

MOGENSEN CE, CHRISTENSEN CK, VITHINGHUS E. The stages in diabetic renal disease with emphasis on the stage of incipient diabetic nephropathy. Diabetes 1983;32:64-78.

MUTSAERS SE, BISHOP JE, MCGROUTHER G, LAURENT GJ. Mechanisms of tissue repair: from wound healing to fibrosis. Int. J. Biochem. Cell Biol. 1997;29:5-17.

NATIONAL KIDNEY FOUNDATION. DOQI 2000. Chronic Kidney Disease: Evaluation, Classification and Stratification. [on-line]. Available in: http://www.kidney.org/professionals.

NERLICH A, SCHLEICHER E. Immunohistochemical localization of extracellular matrix components in human diabetic glomerular lesions. Am. J. Pathol.1991;139:889-99.

NICHOLAS SB, AGUINIGA E, REN Y, KIM J, WONG J, GOVINDARAJAN N, NODA M, WANG W, KAWANO Y, COLLINS A, HSUEH WA. Plasminogen activator inhibitor-1 deficiency retards diabetic nephropathy. Kidney Int.

NG YY, HUANG TP, YANG WC, CHEN ZP, YANG AH, MU W, NIKOLIC- PATERSON DJ, ATKINS RC, LAN HY. Tubular epithelial-myofibroblast trasdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int. 1998;54:864-76.

OHKUBO Y, KISHIKAWA H, ARAKI E, MIYATA T, ISAMI S, MOTOYOSHI S, KOJIMA Y, FURUYOSHI N, SHICHIRI M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6- years study. Diabetes Res. Clin. Pract. 1995;28:103-17.

PARVING HH, LEHNERT H, BROCHNER-MORTENSEN J, GOMIS R, ANDERSEN S, ARNER P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N. Engl. J. Med.

2001;345:870-8.

PERICO N, BENIGNI A, GABANELLI M, PICCINELLI A, ROG M, DE RIVA C, REMUZZI G. Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats. Diabetes 1992;41:533-8.

PERKINS BA, FICOCIELLO LH, OSTRANDER BE, SILVA KH, WEINBERG J, WARRAM JH, KROLEWSKI AS. Microalbuminuria and the risk of early progressive renal function decline in type 1 diabetes. J. Am. Soc. Nephrol.

POULSOM R, FORBES SJ, HODIVALA-DILKE K, RYAN E, WYLES S, NAVARATNARASAH S, JEFERRY R, HUNT T, ALLISON M, COOK T, PUSEY C, WRIGHT NA. Bone marrow contributes to renal parenchymal turnover and regeneration. J. Pathol. 2001;195:229-35.

RAZZAQUE MS, KOJI T, TAGUCHI T, HARADA T, NAMANE PK. In situ localization of type III and type IV collagen-expressing cells in human diabetic nephropathy. J. Pathol. 1994;174:131-38.

REMUZZI A, PERICO N, AMUCHASTEGUI CS, MALANCHINI B, MAZERSKA M, BATTAGLIA C, BERTANI T, REMUZZI G. Short and long- term effect of angiotensin II receptor blockade in rats with experimental diabetes. J. Am. Soc. Nephrol. 1993;4:40-9.

REMUZZI A, GAGLIARDINI E, DONADONI C, FASSI A, SANGALLI F, LEPRE MS, REMUZZI G, BENIGNI A. Effect of angiotensin II antagonism on the regression of kidney disease in the rat. Kidney Int. 2002;62:885-94.

ROSSING K, SCHOEDT KJ, JENSEN BR, BOOMSMA F, PARVING HH. Enhaced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney Int. 2006;68-1190-8.

RUGGENENTI P, PERNA A, GHERARDI G, GASPARI F, BENINI R, REMUZZI G. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropaty. Lancet 1998;352:1252-6.

SCHJOEDT KJ, ROSSING K, JUHI TR, BOOMSMA F, ROSSING P, TARNOW L, PARVING HH. Beneficial impact of spironolactone in diabetic nephropathy. Kidney Int. 2005;68:2829-36.

SHANKLAND SJ, LY H, THAI K, SCHOLEY JW. Glomerular expression of tissue inhibitor of metalloproteinase (TIMP-1) in normal and diabetic rats. J. Am. Soc. Nephrol. 1996;7:97-104.

SINGH R, ALAVI N, SINGH AK, LEEHEY DJ. Role of angiotensin II in glucose-induced inhibition of mesangial matrix degradation. Diabetes

1999;48:2066-73.

SOCIEDADE BRASILEIRA DE NEFROLOGIA. [on line]. Censo 2006 para tratamento dialítico crônico. Disponível em: http://www.sbn.org.br.

STACK AG, BLOEMBERGEN WE. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: A cross-sectional study. J. Am. Soc. Nephrol. 2001;12:1516-23.

STEFFES MW, OSTERBY R, CHAVERS B, MAUER SM. Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients. Diabetes 1989;38:1077-81.

STOKES MB, HOLLER S, CUI Y, HUDKINS KL, EITNER F, FOGO A, ALPERS CE. Expression of decorin, biglycan and collagen type I in human renal fibrosing disease. Kidney Int. 2000;57:487-98.

SUZUKI D, MIYAZAKI M, JINDE K, KOJI T, YAGAME M, ENDO M, NOMOTO Y, SAKAI H. In situ hybridization studies of matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-1 and type IV collagen in diabetic nephropathy. Kidney Int. 1997;52:111-19.

TANJI N, MARKOWITZ GS, FU C, KISLINGER T, TAGUCHI A, PISCHETSRIEDER M, STEM D, SCHMIDT AM, D´AGATI VD. Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal diseases. J. Am. Soc. Nephrol.

2000;11:1656-66.

USRD. Annual Data Report. Incidence and Prevalence, 2001. Am. J. Kidney Dis. 2001;38:S37-52.

UTIMURA R, FUJIHARA CK, MATTAR AL, MALHEIROS DMAC, NORONHA IL, ZATZ R. Mychophenolate mofetil prevents the development of glomerular injury in experimental diabetes. Kidney Int. 2003;63:209-16.

VALLON V, WEAD LM, BLANTZ RC. Renal hemodynamics and plasma and kidney angiotensin II in established diabetes mellitus in rats: Effect of sodium and salt restriction. J Am Soc Nephrol. 1995;5:1761-67.

VAN DYK DJ, ERMAN A, ERMAN T, CHEN-GAL B, SULKES J, BONER G. Increased serum angiotensin converting enzyme activity in type 1 insulin dependent diabetes mellitus: Its relation to metabolic control and diabetic complications. Eur. J. Clin. Invest. 1994;24:463-67.

VAN VLIET A, BAELDE HJ, VLEMING LJ, DE HEER E, BRUIJN JA. Distribution of fibronectin isoforms in human renal disease. J. Pathol.

2001;193:256-62.

WALLENSTEIN, S; ZUCKER, CL; FLEISS, J.L. Some statistical methods useful in circulation research. Circ. Res. 1980;47:1-9.

WEIGERT C, BRODBECK K, KLOPFER K, HARING HU, SCHLEICHER ED. Angiontensin II induces human TGF-β 1 promoter activation: similarity to hyperglycemia. Diabetologia 2002;45:889-98.

WOLF G, ZIYADEH FN. The role of angiotensin II in diabetic nephropathy. Emphasis on nonhemodynamic mechanisms. Am. J. Kidney Dis.

1997;29:153-63.

ZATZ R, DUNN BR, MEYER TW, ANDERSON S, RENNKE HG, BRENNER BM. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J. Clin. Invest. 1986;77:1925-30.

ZATZ R. A low-cost tail-cuff method for the estimation of mean arterial pressure in conscious rats. Lab. Anim. Sci. 1990;40:198-201.

ZIYADEH FN, SHARMA K, ERICKSEN M, WOLF G. Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor- beta. J. Clin. Invest. 1994;93:536-42.

ZIYADEH FN, HOFFMAN BB, HAN DC, IGLESIAS-DE LA CRUZ MC, HONG SW, ISONO M, CHEN S, MCGOWAN TA, SHARMA K. Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. Proc. Natl. Acad. Sci.