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Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat.
J Renin Angiotensin Aldosterone Syst. 2004 Sep; 5(3):146-51.JR

Abstract

INTRODUCTION

Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor beta 1 (TGF-beta 1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-beta 1 in diabetic rats.

MATERIALS AND METHODS

Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days.

RESULTS

Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-beta1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-beta 1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558).

CONCLUSIONS

Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-beta 1.

Authors+Show Affiliations

Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva 49100, Israel. aerman@clalit.org.ilNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15526251

Citation

Erman, Arie, et al. "Renin-angiotensin System Blockade Prevents the Increase in Plasma Transforming Growth Factor Beta 1, and Reduces Proteinuria and Kidney Hypertrophy in the Streptozotocin-diabetic Rat." Journal of the Renin-angiotensin-aldosterone System : JRAAS, vol. 5, no. 3, 2004, pp. 146-51.
Erman A, Veksler S, Gafter U, et al. Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat. J Renin Angiotensin Aldosterone Syst. 2004;5(3):146-51.
Erman, A., Veksler, S., Gafter, U., Boner, G., Wittenberg, C., & van Dijk, D. J. (2004). Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat. Journal of the Renin-angiotensin-aldosterone System : JRAAS, 5(3), 146-51.
Erman A, et al. Renin-angiotensin System Blockade Prevents the Increase in Plasma Transforming Growth Factor Beta 1, and Reduces Proteinuria and Kidney Hypertrophy in the Streptozotocin-diabetic Rat. J Renin Angiotensin Aldosterone Syst. 2004;5(3):146-51. PubMed PMID: 15526251.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat. AU - Erman,Arie, AU - Veksler,Semyon, AU - Gafter,Uzi, AU - Boner,Geoffrey, AU - Wittenberg,Clara, AU - van Dijk,David Jonathan, PY - 2004/11/5/pubmed PY - 2005/2/16/medline PY - 2004/11/5/entrez SP - 146 EP - 51 JF - Journal of the renin-angiotensin-aldosterone system : JRAAS JO - J Renin Angiotensin Aldosterone Syst VL - 5 IS - 3 N2 - INTRODUCTION: Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor beta 1 (TGF-beta 1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-beta 1 in diabetic rats. MATERIALS AND METHODS: Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days. RESULTS: Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-beta1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-beta 1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558). CONCLUSIONS: Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-beta 1. SN - 1470-3203 UR - https://www.unboundmedicine.com/medline/citation/15526251/Renin_angiotensin_system_blockade_prevents_the_increase_in_plasma_transforming_growth_factor_beta_1_and_reduces_proteinuria_and_kidney_hypertrophy_in_the_streptozotocin_diabetic_rat_ L2 - http://journals.sagepub.com/doi/full/10.3317/jraas.2004.032?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -