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¹ Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA

Recent studies have demonstrated the presence of the (pro)renin receptor (PRR) in the glomerular mesangium and the subendothelial layer of the renal arteries. We hypothesized that diabetes upregulates PRR expression through enhanced angiotensin subtype 1 (AT₁) receptor–NADPH oxidase cascade activity. Using real-time polymerase chain reaction, Western blot analysis and immunostaining, we studied renal localization of the PRR in the streptozotocin-induced diabetic rat model and in response to 1 week of treatment with the AT₁ receptor blocker valsartan (10 mg kg^–1 day^–1), the angiotensin AT₂ receptor blocker PD123319 (0.5 mg kg^–1 day^–1) or the NADPH oxidase inhibitor diphenylene iodonium (DPI; 0.5 mg kg^–1 day^–1) 6 weeks post-induction of diabetes. Both PRR mRNA and protein were expressed constitutively in the kidneys of normal rat renal cortex and medulla, mainly in glomerular mesangium, proximal, distal and collecting tubules. Compared with normal rats (100%), diabetic rats demonstrated an increase in renal PRR mRNA (184%), protein (228%) and immunostaining. Valsartan and DPI prevented the increase in the PRR mRNA (106 and 126%, respectively), protein (97 and 140%, respectively) and immunostaining that was seen in the kidneys of diabetic rats. The AT₂ blocker PD123319 did not have significant effects on PRR mRNA (157%) or protein expression (200%) in the kidneys of diabetic rats. These results demonstrate that the PRR is constitutively expressed in renal glomeruli and tubules. Expression of the PRR is upregulated in diabetes via enhancement of AT₁ receptor–NADPH oxidase activity.

(Received 29 October 2007; accepted after revision 4 January 2007; first published online 11 January 2008)
Corresponding author H. M. Siragy: PO Box 801409, University of Virginia Health System, Charlottesville, VA 22908-1409, USA. Email: hms7a{at}virginia.edu

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				M. K. Raizada and J. F. R. Paton Recent advances in the renin-angiotensin system: angiotensin-converting enzyme 2 and (pro)renin receptor Exp Physiol, May 1, 2008; 93(5): 517 - 518. [Full Text] [PDF]