| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Renal Division of the Department of Internal Medicine, and the Department of Cell Biology-Physiology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, Missouri 63110
Cellular and
molecular events contributing to tubulointerstitial fibrosis of the
kidney during obstructive nephropathy are driven in large part through
increased angiotensin II levels in the obstructed kidney. Angiotensin
converting enzyme inhibition or
AT1 receptor antagonism have been
shown to ameliorate the fibrosis of the kidney due to obstruction of
the ureter. In this investigation, we determine the effects of the
AT2 receptor antagonist PD-123319 on pathophysiological events within the kidneys of rats with unilateral ureteral obstruction. Treatment with PD-123319 was found to exacerbate the increase in interstitial volume and collagen IV matrix score of the
ureteral obstructed kidney. Monocyte/macrophage infiltration of the
injured kidney was no different between treated and untreated animals.
The AT2 receptor antagonist did,
however, inhibit apoptosis of tubular cells, 
-smooth muscle actin
expression within the interstitium, and p53 expression in the ureteral
obstructed kidney. These results suggest that angiotensin II operating
through the AT2 receptor exerts an
antifibrotic effect on the kidney during obstructive nephropathy in
opposition to the profibrotic effects of angiotensin II operating
through the AT1 receptor.
angiotensin II; tubulointerstitial fibrosis; -smooth muscle
actin; monocytes/macrophages; apoptosis
This article has been cited by other articles:
|
|
 |
|
  C. M. Coleman, J. J. Minor, L. E. Burt, B. A. Thornhill, M. S. Forbes, and R. L. Chevalier Angiotensin AT1-receptor inhibition exacerbates renal injury resulting from partial unilateral ureteral obstruction in the neonatal rat Am J Physiol Renal Physiol, July 1, 2007; 293(1): F262 - F268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Joshi and D. M. Guidot The alcoholic lung: epidemiology, pathophysiology, and potential therapies Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L813 - L823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. O. Chen, M. H. Park, M. S. Forbes, B. A. Thornhill, S. C. Kiley, K. H. Yoo, and R. L. Chevalier Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat Am J Physiol Renal Physiol, March 1, 2007; 292(3): F946 - F955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Misseri, D. R. Meldrum, C. A. Dinarello, P. Dagher, K. L. Hile, R. C. Rink, and K. K. Meldrum TNF-{alpha} mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling Am J Physiol Renal Physiol, February 1, 2005; 288(2): F406 - F411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wamsley-Davis, R. Padda, L. D. Truong, C. C. Tsao, P. Zhang, and D. Sheikh-Hamad AT1A-mediated activation of kidney JNK1 and SMAD2 in obstructive uropathy: preservation of kidney tissue mass using candesartan Am J Physiol Renal Physiol, September 1, 2004; 287(3): F474 - F480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Klahr and J. Morrissey Obstructive nephropathy and renal fibrosis Am J Physiol Renal Physiol, November 1, 2002; 283(5): F861 - F875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Armando, M. Jezova, A. V. Juorio, J. A. Terron, A. Falcon-Neri, C. Semino-Mora, H. Imboden, and J. M. Saavedra Estrogen upregulates renal angiotensin II AT2 receptors Am J Physiol Renal Physiol, November 1, 2002; 283(5): F934 - F943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Bagby, L. S. LeBard, Z. Luo, B. E. Ogden, C. Corless, E. D. McPherson, and R. C. Speth ANG II AT1 and AT2 receptors in developing kidney of normal microswine Am J Physiol Renal Physiol, October 1, 2002; 283(4): F755 - F764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Lorenzo, M. Ruiz-Ortega, Y. Suzuki, M. Ruperez, V. Esteban, T. Sugaya, and J. Egido Angiotensin III Activates Nuclear Transcription Factor-{kappa}B in Cultured Mesangial Cells Mainly via AT2 Receptors: Studies with AT1 Receptor-Knockout Mice J. Am. Soc. Nephrol., May 1, 2002; 13(5): 1162 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F. Hilgers and J. F. E. Mann ACE Inhibitors versus AT1 Receptor Antagonists in Patients with Chronic Renal Disease J. Am. Soc. Nephrol., April 1, 2002; 13(4): 1100 - 1108. [Full Text] [PDF]
|
|
|
|
|
|
D. P. Basile, D. Donohoe, K. Roethe, and J. L. Osborn Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function Am J Physiol Renal Physiol, November 1, 2001; 281(5): F887 - F899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zimpelmann and K. D. Burns Angiotensin II AT2 receptors inhibit growth responses in proximal tubule cells Am J Physiol Renal Physiol, August 1, 2001; 281(2): F300 - F308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. P. Lewington, M. Arici, K. P. G. Harris, N. J. Brunskill, and J. Walls Modulation of the renin-angiotensin system in proteinuric renal disease: are there added benefits? Nephrol. Dial. Transplant., May 1, 2001; 16(5): 885 - 888. [Full Text] [PDF]
|
|
|
|
|
|
G. Guo, J. Morrissey, R. McCracken, T. Tolley, H. Liapis, and S. Klahr Contributions of angiotensin II and tumor necrosis factor-{alpha} to the development of renal fibrosis Am J Physiol Renal Physiol, May 1, 2001; 280(5): F777 - F785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. MORRISSEY, G. GUO, R. MCCRACKEN, T. TOLLEY, and S. KLAHR Induction of CD14 in Tubular Epithelial Cells During Kidney Disease J. Am. Soc. Nephrol., September 1, 2000; 11(9): 1681 - 1690. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Gallinat, S. Busche, M. K. Raizada, and C. Sumners The angiotensin II type 2 receptor: an enigma with multiple variations Am J Physiol Endocrinol Metab, March 1, 2000; 278(3): E357 - E374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fukagawa, M. Noda, T. Shimizu, and K. Kurokawa Chronic progressive interstitial fibrosis in renal disease--are there novel pharmacological approaches? Nephrol. Dial. Transplant., December 1, 1999; 14(12): 2793 - 2795. [Full Text] [PDF]
|
|
|
|
|
|
G. Guo, J. Morrissey, R. McCracken, T. Tolley, and S. Klahr Role of TNFR1 and TNFR2 receptors in tubulointerstitial fibrosis of obstructive nephropathy Am J Physiol Renal Physiol, November 1, 1999; 277(5): F766 - F772. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
