Received October 29, 2007
Revised November 19, 2007
Accepted after revision January 4, 2008
ACE2 & RR Themed Issue
(Pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity
Helmy M. Siragy 1*
Jiqian Huang 1
1 UVA
* To whom correspondence should be addressed. E-mail: hms7a{at}virginia.edu.
 |
Abstract |
|---|
Recent studies 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 PCR, western blot analysis and immunostaining, we studied renal localization of the PRR in streptozotocin induced diabetes rat model and in response to one week treatment with the AT1 receptor blocker valsartan (10mg/kg/d), angiotensin AT2 receptor blocker PD123319 (0.5 mg/kg/d) or the NADPH oxidase inhibitor diphenylene iodonium (DPI 0.5mg/kg/d) 6 weeks post induction of diabetes. Both PRR mRNA and protein were expressed constitutively in the kidneys of normal rats renal cortex and medulla, mainly in glomerular mesangium, proximal, distal and collecting tubules. Compared to normal (100%), diabetic rats demonstrated 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 diabetic rats kidneys. AT2 blocker PD did not have significant effects on PRR mRNA (157%) or protein (200%) expression in the kidney. These results demonstrate that PRR is constitutively expressed in renal glomeruli and tubules. PRR expression is upregulated in diabetes via enhancement of the AT1 receptor-NADPH oxidase activity.
Key Words:
Diabetes, Kidney, Receptor
