Inhibition of aminopeptidase A activity causes an acute albuminuria in mice: an angiotensin II-mediated effect?

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
S MentzelR A Koene

Abstract

The hydrolase aminopeptidase A is an important regulator of the renin-angiotensin system, since it inactivates its most vasoactive component angiotensin II (Ang II). A single i.v. injection of a monoclonal antibody against mouse aminopeptidase A (ASD-4) induces a membranous-like glomerulonephritis in mice, characterized by an acute albuminuria, that is not dependent on complement, the coagulation system, or inflammatory cells. We hypothesized that this albuminuria is the consequence of a reduction in aminopeptidase A enzyme activity, that might subsequently lead to an increase in Ang II levels. Aminopeptidase A enzyme activity was analysed in vitro by a fluorimetric enzyme assay and in vivo by enzyme histochemistry. The role of Ang II in the induction of albuminuria in this model was studied by measuring the renal aminopeptidase A mRNA expression in our model by a competitive PCR assay as an indirect measure of Ang II levels. In addition, the role of Ang II in this model was studied by preventing the formation of Ang II with the angiotensin-converting enzyme inhibitor enalapril or by blocking of the Ang II receptor with the AT1 receptor antagonist losartan. Only antibodies that were able to inhibit the aminopeptidase A enzyme a...Continue Reading

Citations

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