HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/5/F1069    most recent 00345.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Sharma, K. Articles by Inscho, E. W. Search for Related Content PubMed PubMed Citation Articles by Sharma, K. Articles by Inscho, E. W.

TRANSLATIONAL PHYSIOLOGY

TGF- impairs renal autoregulation via generation of ROS

¹Dorrance Hamilton Research Laboratories, Division of Nephrology, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania; and ²Department of Physiology, Medical College of Georgia, Augusta, Georgia

Submitted 14 September 2004 ; accepted in final form 29 December 2004

Impaired autoregulation in chronic kidney disease can result in elevation of glomerular capillary pressure and progressive glomerular damage; however, the factors linking chronic glomerular disorders to impaired autoregulation have not been identified. We tested the hypothesis that the cytokine most closely associated with progressive glomerular disease, transforming growth factor (TGF)-, may also attenuate autoregulation. Kidneys from normal rats were prepared for videomicroscopy, using the blood-perfused juxtamedullary nephron technique. Autoregulatory responses were measured under control conditions and during superfusion with TGF-₁ (10 ng/ml). Control afferent arteriolar diameter averaged 18.4 ± 1 µm and significantly decreased to 16.3 ± 0.9 and 13.2 ± 0.8 µm at perfusion pressures of 130 and 160 mmHg, respectively. In the presence of TGF-₁, autoregulatory responses were completely blocked. In similar experiments performed using PDGF-BB (10 ng/ml) and HGF (25 ng/ml), the normal autoregulatory response was not affected. In vitro studies, using isolated preglomerular vascular smooth muscle cells, revealed that exposure to TGF-₁ stimulated a rapid increase in reactive oxygen species (ROS) that was inhibited by NADPH oxidase inhibitors. In situ studies, with dihydroethidium staining, revealed a marked increase in renal vessel ROS production on exposure to TGF-₁. Pretreatment of the juxtamedullary afferent arterioles with tempol, a ROS scavenger, or with apocynin, a NADPH oxidase inhibitor, prevented the impaired autoregulation induced by TGF-₁. These data reveal a novel hemodynamic pathway by which TGF- could lead to progressive glomerular injury by impairing normal renal microvascular function.

renal hemodynamics; kidney disease; hypertension; growth factors; oxidative stress; NADPH oxidase

E. W. Inscho, Dept. of Physiology, School of Medicine, Medical College of Georgia, 1120 15th St., Augusta, GA 30912-3000 (E-mail: EINSCHO{at}mail.mcg.edu)

This article has been cited by other articles:

				X. F. Wei, Q. G. Zhou, F. F. Hou, B. Y. Liu, and M. Liang Advanced oxidation protein products induce mesangial cell perturbation through PKC-dependent activation of NADPH oxidase Am J Physiol Renal Physiol, February 1, 2009; 296(2): F427 - F437. [Abstract] [Full Text] [PDF]

				E. W. Inscho Mysteries of Renal Autoregulation Hypertension, February 1, 2009; 53(2): 299 - 306. [Full Text] [PDF]

				C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]

				P. Pacher, K. Sharma, G. Csordas, Y. Zhu, and G. Hajnoczky Uncoupling of ER-mitochondrial calcium communication by transforming growth factor-{beta} Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1303 - F1312. [Abstract] [Full Text] [PDF]

				A. A. Elmarakby, J. E. Quigley, J. J. Olearczyk, A. Sridhar, A. K. Cook, E. W. Inscho, D. M. Pollock, and J. D. Imig Chemokine Receptor 2b Inhibition Provides Renal Protection in Angiotensin II Salt Hypertension Hypertension, December 1, 2007; 50(6): 1069 - 1076. [Abstract] [Full Text] [PDF]

				L. Gnudi, S. M. Thomas, and G. Viberti Mechanical Forces in Diabetic Kidney Disease: A Trigger for Impaired Glucose Metabolism J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2226 - 2232. [Abstract] [Full Text] [PDF]

				P. Meier, J. Rossert, P.-F. Plouin, and M. Burnier Atherosclerotic renovascular disease: beyond the renal artery stenosis Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1002 - 1006. [Full Text] [PDF]

				A. K. Khanna and G. M. Pieper NADPH oxidase subunits (NOX-1, p22phox, Rac-1) and tacrolimus-induced nephrotoxicity in a rat renal transplant model Nephrol. Dial. Transplant., February 1, 2007; 22(2): 376 - 385. [Abstract] [Full Text] [PDF]

				L. Gnudi and G. Viberti The link between mechanical stretch and glucose metabolism--a conceptual advance in understanding diabetic (and non diabetic?) renal disease Nephrol. Dial. Transplant., February 1, 2007; 22(2): 318 - 321. [Full Text] [PDF]

				C. Ruster and G. Wolf Renin-Angiotensin-Aldosterone System and Progression of Renal Disease J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2985 - 2991. [Abstract] [Full Text] [PDF]

				T. A. McGowan, S. R. Dunn, B. Falkner, and K. Sharma Stimulation of Urinary TGF-{beta} and Isoprostanes in Response to Hyperglycemia in Humans Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 263 - 268. [Abstract] [Full Text] [PDF]

				G. Wolf 'As time goes by': angiotensin II-mediated transactivation of the EGF receptor comes of age Nephrol. Dial. Transplant., October 1, 2005; 20(10): 2050 - 2053. [Full Text] [PDF]