Does angiotensin (1-7) contribute to the anti-proteinuric effect of ACE-inhibitors.
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.
Department of Clinical Pharmocology, Division of Nephrology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, Groningen, The Netherlands. e.a.van.der.wouden@med.umcg.nl
Els A
EA
van der Wouden
Robert H
RH
Henning
Leo E
LE
Deelman
Anton J M
AJ
Roks
Frans
F
Boomsma
Dick
D
de Zeeuw
D000803:Angiotensin I / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003401:Creatine / Q000097:blood; D003404:Creatinine / Q000097:blood; D004317:Doxorubicin; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
C092006:7-Ala-angiotensin (1-7); D000806:Angiotensin-Converting Enzyme Inhibitors; D000903:Antibiotics, Antineoplastic; D010446:Peptide Fragments; D000804:Angiotensin II; D004317:Doxorubicin; D000803:Angiotensin I; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A; C118790:angiotensin I (1-7); D003401:Creatine