![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL
Agonist Provides Superior Renal Protection versus Angiotensin-Converting Enzyme Inhibition in a Rat Model of Type 2 Diabetes with Obesity
Department of Physiology, West Virginia University, Morgantown, West Virginia (C.B., G.F., K.E.); and F. Hoffmann-La Roche AG, Basel, Switzerland (E.-A.A.)
The inbred obese Zucker (ZDF/Gmi, fa/fa) rat develops severe hyperglycemia and also exhibits severe renal disease. In this study, we compared the relative benefits of long-term treatment with angiotensin-converting enzyme inhibition (ACEI) to a peroxisome proliferator-activated receptor 
(PPAR) agonist. Four groups of obese inbred Zucker rats were studied over a 6-month observation period; untreated animals, rats treated with ACEI alone, rats treated with PPAR agonist alone, and rats treated with a combination of ACEI and PPAR agonist. PPAR agonist treatment normalized plasma glucose and led to massive increases in body weight. Both ACEI and PPAR agonist were effective in reducing the proteinuria and glomerular and tubular kidney damage. However, the PPAR agonist exerted superior renal protection compared with ACEI, in this model of spontaneously occurring chronic renal disease in the diabetic, obese inbred Zucker rat. Of note, although ACEI lowered blood pressure, there was no difference in glomerular blood pressure in any group at the end of the study. The glomerular filtration rate (GFR) was improved by ACEI with a borderline effect of PPAR agonist alone. A mild additive protection on GFR and tubulointerstitial damage was seen with the combination. Based on the literature it is likely that the superior protection by PPAR agonist versus glomerular and tubular damage as well as proteinuria extends beyond glycemic and lipidmic control and also reflects direct, protective intrarenal actions of the PPAR agonists.
Address correspondence to: Dr. Chris Baylis, P.O. Box 9229, West Virginia University Health Sciences Ctr., 1 Medical Center Dr., Morgantown, WV 26506-9229. E-mail: cbaylis{at}wvu.edu
This article has been cited by other articles:
|
|
 |
|
  S. S. Ghosh, H. D. Massey, R. Krieg, Z. A. Fazelbhoy, S. Ghosh, D. A. Sica, I. Fakhry, and T. W. B. Gehr Curcumin ameliorates renal failure in 5/6 nephrectomized rats: role of inflammation Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1146 - F1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Toblli, M. G. Ferrini, G. Cao, D. Vernet, M. Angerosa, and N. F. Gonzalez-Cadavid Antifibrotic effects of pioglitazone on the kidney in a rat model of type 2 diabetes mellitus Nephrol. Dial. Transplant., March 17, 2009; (2009) gfp103v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Ko, Y. S. Kang, S. Y. Han, M. H. Lee, H. K. Song, K. H. Han, H. K. Kim, J. Y. Han, and D. R. Cha Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2750 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ingbir, I. F. Schwartz, A. Shtabsky, I. Filip, R. Reshef, T. Chernichovski, N. Levin-Iaina, U. Rozovski, Y. Levo, and D. Schwartz Rosiglitazone improves aortic arginine transport, through inhibition of PKC{alpha}, in uremic rats Am J Physiol Renal Physiol, August 1, 2008; 295(2): F471 - F477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ruan, F. Zheng, and Y. Guan PPARs and the kidney in metabolic syndrome Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1032 - F1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. C. Kopp, M. Z. Cicha, and M. A. Yorek Impaired responsiveness of renal sensory nerves in streptozotocin-treated rats and obese Zucker diabetic fatty rats: role of angiotensin Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R858 - R866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Baylis Nitric oxide deficiency in chronic kidney disease Am J Physiol Renal Physiol, January 1, 2008; 294(1): F1 - F9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Griffin, M. Abu-Naser, I. Abu-Amarah, M. Picken, G. A. Williamson, and A. K. Bidani Dynamic blood pressure load and nephropathy in the ZSF1 (fa/facp) model of type 2 diabetes Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1605 - F1613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yousefipour, H. Hercule, L. Truong, A. Oyekan, and M. Newaz Ciglitazone, a Peroxisome Proliferator-Activated Receptor {gamma} Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A2 in Glycerol-Induced Acute Renal Failure J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 461 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, H. Meng, Z.-H. Li, Z. Shu, X. Ma, and B.-X. Zhang Regulation of STIM1, store-operated Ca2+ influx, and nitric oxide generation by retinoic acid in rat mesangial cells Am J Physiol Renal Physiol, March 1, 2007; 292(3): F1054 - F1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Boulanger, R. Mansouri, J. F. Gautier, and D. Glotz Are peroxisome proliferator-activated receptors new therapeutic targets in diabetic and non-diabetic nephropathies? Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2696 - 2702. [Full Text] [PDF]
|
|
|
|
 |
|
 M C. Lansang, C. Coletti, S. Ahmed, M. S Gordon, and N. K Hollenberg Effects of the PPAR-{gamma} Agonist Rosiglitazone on Renal Haemodynamics and the Renin-Angiotensin System in Diabetes Journal of Renin-Angiotensin-Aldosterone System, September 1, 2006; 7(3): 175 - 180. [Abstract] [PDF]
|
|
|
|
|
|
J. Weissgarten, S. Berman, S. Efrati, M. Rapoport, Z. Averbukh, and L. Feldman Apoptosis and proliferation of cultured mesangial cells isolated from kidneys of rosiglitazone-treated pregnant diabetic rats Nephrol. Dial. Transplant., May 1, 2006; 21(5): 1198 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Hall Prevention of Progression in Diabetic Nephropathy Diabetes Spectr, January 1, 2006; 19(1): 18 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, X. Wen, B. C. Spataro, K. Hu, C. Dai, and Y. Liu Hepatocyte Growth Factor Is a Downstream Effector that Mediates the Antifibrotic Action of Peroxisome Proliferator-Activated Receptor-{gamma} Agonists J. Am. Soc. Nephrol., January 1, 2006; 17(1): 54 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Abrass Overview: Obesity: What Does It Have to Do with Kidney Disease? J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2768 - 2772. [Full Text] [PDF]
|
|
|
|
|
|
Y. Guan Peroxisome Proliferator-Activated Receptor Family and Its Relationship to Renal Complications of the Metabolic Syndrome J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2801 - 2815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wu, Y. Zhang, N. Wang, L. Davis, G. Yang, X. Wang, Y. Zhu, M. D. Breyer, and Y. Guan Liver X receptor-{alpha} mediates cholesterol efflux in glomerular mesangial cells Am J Physiol Renal Physiol, November 1, 2004; 287(5): F886 - F895. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
