Glomerular angiotensinase A in the rat: Increase of enzyme activity following renal ablation

Abstract

Angiotensinase A (aminopeptidase A; ATA) is an angiotensin II splitting exopeptidase, which is localized in endothelial and epithelial cells of the glomerular tuft. In order to investigate the influence of a reduction in renal mass on enzyme activity, ATA activity was measured in isolated rat glomeruli five and 14 weeks after 1-1/3 nephrectomy. Glomerular ATA activity in remnant kidneys increased significantly after five weeks following ablation compared with glomeruli of two kidney control rats (5.34 +/- 4.02 vs. 1.71 +/- 1.96 mU/mg protein, P less than 0.05). After 14 weeks, however, this difference was no longer present. Treatment of rats with enalapril or saralasin inhibited the increase of ATA seen five weeks after renal ablation, whereas indomethacin had no effect on enzyme activity. Furthermore, normal two kidney rats, treated with furosemide, revealed a higher glomerular ATA than two kidney controls (5.5 +/- 2.64 vs. 2.1 +/- 1.7 mU/mg protein, P less than 0.05). In vitro superfusion of isolated glomeruli with enalaprilate or furosemide from rats after renal ablation did not influence enzyme activity, however, superfusion with 0.05 mM angiotensin II or 0.05 mM saralasin significantly reduced ATA. Our results suggest that glomerular ATA might be involved in the early regulation of the intrarenal renin-angiotensin system and could modify glomerular adaptation to reduce renal mass by affecting angiotensin II degradation.

Receptor‐mediated induction of aminopeptidase A (APA) of human glomerular epithelial cells (HGEC) by glucocorticoids

“…Induction of peptidases and increase in immunogiobulin E synthesis may represent mechanisms whereby these proteins are regulated under physiologic conditions and the therapeutic actions of glucocorticoids are mediated+ Kidney APA regulation has not been extensively studied, APA is Io- calized in the epithelial and endothelial cells of the glomerular tuft and probably modulates giomerular functions by inactivating A !!. In keeping with this possibility, Wolf et al [14] suggested that glomerular APA might be involved in the early regulation of the intrarehal renin-angiotensin system and modify glomerular adaptations after renal mass ablation. Several peptidascs which metabolize A !…”

Kidney Aminopeptidase A and Hypertension, Part I

“…Wolf et al 51,52 reported that APA activity was increased in partial remnant kidneys. Ang II levels are known to be elevated in this model, and ACE inhibition prevented the increase in kidney APA levels.…”

Early diagnosis of acute kidney injury

“…The maximum IgG elimination occurred at the same time as the tubular damage, whereas the maximum ATA elimination occurred 1 day earlier. This result shows that the increased permeability large molecules such as IgG (molecular weight 150 kDalton) occurs later than the actual damage to the cellular structures (endothelium) [16,19].…”

“…Patients with blood products (median, range) 15 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Patients with antibiotic therapy 40…”

“…The compensatory rise in ATA activity within the endothelia and podocytes of the residual glomeruli may have prevented certain metabolic effects [9]. The ATA as a physiologic marker of glomerular integrity is a measure of the occurring damage [16]. These damage do not necessarily need to be functionally effective, and as such, one frequently One day later (3 days before AKI) other glomerular variables (IgG, Alb) were found to be pathologic, along with THP, as markers for the early distal tubule and total protein values ( Table 2).…”