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1 Department of Medicine, Veterans Affairs Hospital, Hines, IL, USA; Department of Medicine, Loyola University Stritch School of Medicine, Maywood, IL, USA
2 Hektoen Institute for Medical Research, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: dleehey{at}lumc.edu.
Recent evidence suggests that the intrarenal renin-angiotensin system (RAS) may play an important role in the development of glomerular changes associated with diabetic nephropathy. In this study, the glomerular RAS was examined in male Sprague-Dawley rats made diabetic with streptozotocin (STZ), and the findings compared to those obtained in control non-diabetic rats. In diabetic rat glomerular extracts, angiotensinogen and angiotensin II (Ang II) levels were increased significantly by 2.2- and 1.9-fold, respectively, compared with non-diabetic controls. No significant differences in angiotensin I (Ang I) and angiotensin-converting enzyme (ACE) levels were observed between these groups. The HPLC analysis of the glomerular extracts demonstrated that exogenous Ang I was converted into various angiotensin (Ang) peptides including Ang II, Ang(1-9) and Ang(1-7). A significant increase in formation of Ang II from exogenous Ang I was observed in STZ rats compared to control rats. Pre-incubation of glomerular extracts with captopril resulted in a 20-30% decrease in Ang II conversion from exogenous Ang I in diabetic and control rats. The possible role of Ang(1-9) in formation of Ang II was examined by HPLC. Exogenous Ang(1-9) in glomerular extracts was converted into Ang II, this conversion being significantly higher in STZ rats than in control rats. These findings provide new information that Ang(1-9) is produced in rat glomerular extracts, can be converted to Ang II, and that this conversion is also stimulated in diabetic rat glomeruli. Thus, this study demonstrates that in diabetic rats, glomerular Ang II levels are increased due to an increase in angiotensinogen and an increase in the formation of Ang II.
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