Local induction of angiotensin-converting enzyme in the kidney as a mechanism of progressive renal diseases

Abstract

Local induction of angiotensin-converting enzyme as a mechanism contributing to progressive renal disease. Angiotensin Converting Enzyme (ACE) or Kininase II has a pivotal role determining the local activity of the renin angiotensin and kallikrein kinin systems. Angiotensin II (Ang II), a main hormone of the renin system, has a well established participation as a renal injury agent in models of renal disease with tubulointerstitial fibrosis. Although, since its discovery, ACE has been known to convert Ang I to Ang II, and to inactivate bradykinin (BK), only recently has been emerged evidence for a role of BK with renal protective and antifibrotic effects opposing Ang II. Pertinent to the tubulointerstitial injury, where infiltration and proliferation of macrophages and fibroblast occur, ACE also regulates the levels of the natural hemoregulatory peptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). Owing the importance of tissue ACE, its distribution was studied in several models of renal injury. The results showed increased ACE in proximal tubules and ACE induction in the cell infiltrated tubulointerstitium (macrophages and myofibroblasts) of injured kidneys from hypokalemic, Goldblatt hypertensive, Ang II and phenylefrine infused rats, and in both human diabetic and membranous nephropathies. ACE, in addition to Ang II generation, may play a pathogenic role through the hydrolysis of BK and Ac-SDKP. Thus, local increase in ACE can be a novel mechanism involved in tubulointerstitial renal injury, providing, from an anatomical ground, a pathological basis for the putative deleterious effect of ACE in the diseased kidneys, and the beneficial effect of ACE inhibition.

Dietary Potassium Downregulates Angiotensin-I Converting Enzyme, Renin, and Angiotensin Converting Enzyme 2

“…In the kidneys from control rats ( Figures 1A, B), ACE was localized in proximal straight tubules. The immunoperoxidase signal was mainly present in the apical domain; scarce or none immunostaining was seen in the cytoplasm and no staining was observed at the basolateral domain, as reported previously (Vio and Jeanneret, 2003). The immunoperoxidase signal was markedly reduced in the high potassium diet group ( Figures 1C, D) compared to the control diet group.…”

β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats

“…Moreover, in vitro studies have shown that Ang II stimulates fibronectin, TGF- β , CTGF, and PAI-1 synthesis [ 11 ]. Several models of kidney disease in both rodents and humans display local induction of the angiotensin converting enzyme (ACE) which is a well-known enzyme capable of forming Ang II from Ang I, providing an explanation for the elevated renal levels of Ang II in several pathological conditions [ 12 ]. In fact, ACE inhibitors (ACEi) or Ang II receptor antagonists are widely used for the treatment of the hypertension as they are known to have antifibrotic effects on the kidney [ 13 ].…”

Effect of Redox Modulating NRF2 Activators on Chronic Kidney Disease

“…Activation of AT1 receptor by angiotensin II administration generated a higher level of superoxide in CKD animals than that of the normal animals [19,26]. A local increase of angiotensin-converting enzyme (ACE) in the kidney was associated with the progress of tubulointerstitial renal injury by hypokalemia, hypertension, and angiotensin II infusion in rats [27].…”