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Does Angiotensin (1-7) Contribute to the Antiproteinuric Effect of ACE-inhibitors?

Department of Clinical Pharmacology, University of Groningen, E.A.van.der.Wouden{at}med.umcg.nl

Robert H Henning

Department of Clinical Pharmacology, University of Groningen

Leo E Deelman

Department of Clinical Pharmacology, University of Groningen

Anton JM Roks

Department of Clinical Pharmacology, University of Groningen

Frans Boomsma

Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Dick de Zeeuw

Department of Clinical Pharmacology, University of Groningen, Division of Nephrology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Angiotensin-converting enzyme inhibitors (ACE-I) reduce proteinuria and protect the kidney in proteinuric renal disease. During ACE-I therapy, circulating levels of angiotensin (1-7) [Ang (1-7)] are increased. As cardiac and renal protective effects of Ang (1-7) have been reported, we questioned whether Ang (1-7) contributes to the antiproteinuric effects of ACE-I treatment.

Therefore, we evaluated whether Ang (1-7) infusion reduces proteinuria in a rat model of adriamycin-induced renal disease. In addition, the effect of a selective Ang (1-7) blocker, [D-Ala⁷]-Ang (1-7) (A779), was investigated in rats treated with the ACE-I, lisinopril (LIS). Six weeks after induction of proteinuria, therapy was started in four different groups: control, Ang (1-7), LIS, and LIS+A779. After two weeks, the rats were sacrificed. Six weeks after injection of adriamycin, the rats

had developed proteinuria of 323±40 mg/24 hours. The proteinuria remained stable in the control group and in the Ang (1-7) group, but was reduced in both LIS and LIS+A779-treated groups. Similarly, blood pressure (BP) was unchanged in the control and the Ang (1-7) groups, but reduced in both the LIS and the LIS+A779 groups. Plasma levels of Ang (1-7) were increased in the Ang (1-7) and in both LIS-treated groups.

We conclude that systemic Ang (1-7) plays no major role in the antiproteinuric and BPlowering effects of ACE-I in this rat model of adriamycin-induced nephrosis.

Key Words: Angiotensin (1-7) • ACE-inhibitors • Proteinuria • BP

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 6, No. 2, 96-101 (2005)
DOI: 10.3317/jraas.2005.016


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