Angiotensin I‐converting enzyme in isolated human glomeruli

Abstract

Angiotensin I-converting enzyme (ACE) activity was measured with hippurylhistidylleucine as a substrate in isolated human glomeruli. The mean level was 2.2k0.47 mIU/mg glomerular protein. S9780, a newly designed competitive inhibitor of ACE, inhibited this activity by 85% at 0.3 PM. PH]S9780 specifically bound to isolated human glomeruli. The & value and the number of sites were 23 nM and 83 fmol/mg, respectively. The prodrug, S9490, and Captopril were less potent than S9780 in displacing rH]S9780 from its binding sites. Angiotensin I had no effect. Binding of PH]S9780 was inhibited after preincubation of the glomeruli with a specific polyclonal anti-human ACE antibody. These results demonstrate that ACE is present in human adult glomeruli.

A Reliable Radiometric Assay for the Determination of Angiotensin I-Converting Enzyme Activity in Urine

“…The absence of a correlation between this urinary enzymatic activity and proteinuria, and even more the lack of dependence of this activity on the indices of glomerular function, such as creatininuria or albuminuria, eliminate the possibility of a passage of the plasmatic enzyme throughout the glomerular filter. Damage of renal glomeruli cannot explain a significant enzymuria, since glomerular epithelial and endothelial cells contain only a little angiotensin-converting enzyme (18,19). Thus, in agreement with other authors (3, 4), we conclude that urinary angiotensin-converting enzyme is of tubular origin, as in the case of most enzymurias (20).…”

Bradykinin stimulates production of inositol (1,4,5) trisphosphate in cultured mesangial cells of the rat via a BK2‐kinin receptor

“…In addition, we found that BK potentiates IP3 formation by 173 + 15% within 20s, whereas on intact glomeruli (Sekar et al, 1990) only a 47 + 10% increase in total inositides was observed within 5min in response to the same concentration of BK (0.1 gM). Although different methodologies are used to assess inositide breakdown, it should be noted that intact glomeruli contain kininase II (Chancel et al, 1987) which could be responsible for a bradykinin degradation that was not assessed in the present investigation (Sekar et al, 1990). All these aspects may explain the difference in the intensity of the BK-induced IP3 formation between our results and those of a recent study performed on intact glomeruli (Sekar et al, 1990).…”

Comparative Regional Distribution of Angiotensin-I-Converting Enzyme in the Rat, Rabbit, Dog, Monkey and Human Kidneys

“…These differences may account for the well-documented differences of anatomical and physiological properties of superficial versus juxtameduilary nephrons [1,2,32] and for interspecies variation in func tional reaction to modification of dietary sodi um intake (since sodium restriction increases the activity of the renin-angiotensin system): in rats on low-sodium diet, whole kidney GFR was associated with a 38% decrease in the fil tration rate of superficial nephrons while the filtration in the juxtameduilary nephrons in creased by 250% as compared to controls [33]: on the other hand, much fewer marked var iations between superficial and juxtameduilary nephrons were seen in the rabbit [34]. Further more, we showed that human isolated glome ruli were able to bind Perindopril (a new ACE inhibitor) while isolated rat glomeruli were not [10]. These observations may in part be related to differences in intrarenal ACE distribution observed in our study, which may lead to dif ferences of the renal site of response to stim ulation or inhibition of the renin angiotensin system.…”

“…ACE has been localized in the kidney using immunohistochemical techniques with both light and electron microscopy [6][7][8]. Although most authors found ACE only in the proximal tubules, others detected ACE activ ity in the distal tubules of hog kidney [7], in cultured glomerular endothelial cells [9], and in the glomerulus of the human [10] and the rabbit [II] kindey. Physiological studies indi cate that ACE is present in the nephron at the level of distal tubules in dogs [12] while in the rat [13] or in the rabbit [14] an increasing gra dient of ACE activity is observed along the proximal tubule and no significant ACE level is seen in other nephron segments.…”