Does angiotensin (1-7) contribute to the anti-proteinuric effect of ACE-inhibitors.

Abstract

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 anti-proteinuric 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 anti-proteinuric and BPlowering effects of ACE-I in this rat model of adriamycin-induced nephrosis.

• Authors: Els A van der Wouden, Robert H Henning, Leo E Deelman, Anton J M Roks, Frans Boomsma, Dick de Zeeuw
• Journal: Journal of the renin-angiotensin-aldosterone system : JRAAS (J Renin Angiotensin Aldosterone Syst) Vol. 6 Issue 2 Pg. 96-101 (Sep 2005) ISSN: 1470-3203 [Print] England
• PMID: 16470489 (Publication Type: Journal Article)

Chemical References

• 7-Ala-angiotensin (1-7)
• Angiotensin-Converting Enzyme Inhibitors
• Antibiotics, Antineoplastic
• Peptide Fragments
• Angiotensin II
• Doxorubicin
• Angiotensin I
• Creatinine
• Peptidyl-Dipeptidase A
• angiotensin I (1-7)
• Creatine

Topics

• Angiotensin I (blood, pharmacology, physiology)
• Angiotensin II (analogs & derivatives, blood, pharmacology)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Antibiotics, Antineoplastic
• Blood Pressure (drug effects, physiology)
• Body Weight (physiology)
• Creatine (blood)
• Creatinine (blood)
• Doxorubicin
• Male
• Peptide Fragments (blood, pharmacology, physiology)
• Peptidyl-Dipeptidase A (blood)
• Proteinuria (chemically induced, drug therapy, physiopathology)
• Rats
• Rats, Wistar