Angiotensinase activities in the kidney of renovascular hypertensive rats

Prieto, Isabel; Hermoso, Francisco; Gasparo, Marc de; Vargas, Félix; Alba, Francisco; Segarra, Ana Belén; Banegas, Inmaculada; Ramı́rez, Manuel

doi:10.1016/s0196-9781(03)00121-9

Cited by 20 publications

(33 citation statements)

References 32 publications

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“…It is logical to postulate that the redistribution of APN out of the apical membranes, or its inhibition, may reflect a compensatory response to reduce ANG III degradation rate in response to reduced ANG II formation during captopril treatment. Related to this point, angiotensin receptor blocker valsartan reduces membrane APN activity in the renal cortex (43). Myosin II-A is a conventional class II nonmuscle myosin heavy chain encoded by the Myh9 gene (47).…”

Section: Discussionmentioning

confidence: 99%

Effects of ACE inhibition on proximal tubule sodium transport

Leong¹,

Devillez²,

Sandberg³

et al. 2006

American Journal of Physiology-Renal Physiology

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Angiotensin-converting enzyme (ACE) inhibitors such as captopril, which block ANG II formation, are commonly used for treatment of hypertension. There is substantial evidence that the proximal tubule (PT) is a primary target site for captopril but the molecular mechanisms for its action in PT are not well defined. The aim of this study was to determine the physiological and molecular changes in PT provoked by acute captopril treatment in the absence of changes in blood pressure or glomerular filtration rate (GFR). Captopril (infused at 12 microg/min for 20 min) did not change blood pressure or GFR but induced an immediate (<10 min) increase in PT flow measured with a nonobstructive optical method (to 117 +/- 14% of baseline) along with a rapid diuresis from 2.1 +/- 0.6 mg/min (baseline) to 3.7 +/- 0.9 mg/min (captopril). Captopril also provoked a significant retraction of PT Na(+)/H(+) exchanger isoform 3 (NHE3), NHE regulatory factor (NHERF)-1, myosin-VI, and Na(+)-P(i) cotransporter type 2 (NaPi2), but not ACE, out of apical microvillus-enriched membranes. Proteomic analysis with MALDI-TOF MS revealed an additional eight abundant membrane-associated proteins that redistributed out of the microvillus-enriched membrane during captopril treatment: megalin, myosin II-A, clathrin, aminopeptidase N, DPPIV, ezrin, moesin, and vacuolar H(+)-ATPase subunit beta(2). In summary, captopril can rapidly depress PT reabsorption in the absence of a change in GFR or BP and provokes the redistribution of a set of transporters and transporter-associated proteins that likely participate in the decrease in PT reabsorption and may also contribute to the blood pressure-lowering effect of ACE inhibitors.

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Section: Discussionmentioning

confidence: 99%

Effects of ACE inhibition on proximal tubule sodium transport

Leong¹,

Devillez²,

Sandberg³

et al. 2006

American Journal of Physiology-Renal Physiology

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“…The results of these studies demonstrated that after treatment with the AT 1 receptor antagonist valsartan, significant differences between normotensive and hypertensive animals were observed in the kidney [109,110] and in the atrium, lung, ventricle, and aorta [111]. These results suggest a close relationship between aminopeptidase activity and the pathogenesis of hypertension in its different forms.…”

Section: Working Hypothesismentioning

confidence: 99%

Role of central and peripheral aminopeptidase activities in the control of blood pressure: a working hypothesis

et al. 2008

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Although there is a large body of knowledge on protein synthesis, the available data on protein catabolism, although quite substantial, are still inadequate. This is due to the marked differences in the activity of proteolytic enzymes, compounded by different substrate specificities and multiple environmental factors. Understanding enzyme behavior under physiological and pathological conditions requires the identification of specific proteolytic activities, such as aminopeptidases, as able to degrade certain peptidergic hormones or neuropeptides. Another requirement is the isolation, purification and characterization of the enzymes involved. In addition, systematic studies are needed to determine each enzyme's subcellular location, tissue distribution, and the influence of environmental factors such as diurnal rhythm, age, gender, diet, cholesterol, or steroids. Central and peripheral aminopeptidases may play a role in the control of blood pressure by coordinating the effect of the different peptides of the renin-angiotensin system cascade, acting through the AT(1), AT(2), and AT(4) receptors. Our review of the available data suggests the hypothesis that cholesterol or steroids, particularly testosterone, significantly influence aminopeptidase activities, their substrate availability and consequently their functions. These observations may have relevant clinical implications for a better understanding of the pathophysiology of cardiovascular diseases, and thus for their treatment with aminopeptidase inhibitors.

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“…In the Goldblatt two-kidney, one-clip model of salt-sensitive hypertension, greater membrane-bound Anpep activity is present in the cortex of the nonclipped kidney (43). We found that Anpep transcript abundance, protein expression, and activity are greater in the kidneys of Dahl salt-resistant (SR/Jr) vs. Dahl salt-sensitive (SS/Jr) and Sprague-Dawley (SD) rat strains (16).…”

mentioning

confidence: 80%

Aminopeptidase N reduces basolateral Na⁺-K⁺-ATPase in proximal tubule cells

Kotlo¹,

Shukla²,

Tawar³

et al. 2007

American Journal of Physiology-Renal Physiology

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Aminopeptidase N/CD13 (Anpep) is a membrane-bound protein that catalyzes the formation of natriuretic hexapeptide angiotensin IV (ANG IV) from ANG III. We previously reported that Anpep is more highly expressed in the kidneys of Dahl salt-resistant (SR/Jr) than salt-sensitive (SS/Jr) rats, Anpep maps to a quantitative trait locus for hypertension, and that the Dahl SR/Jr rat contains a functional polymorphism of the gene. This suggests that renal Anpep may be linked to salt sensitivity; however, its effect on renal Na handling has not been determined. Here, we examined regulation of basolateral Na(+)-K(+)-ATPase, a preeminent basolateral Na(+) transporter in proximal tubule cells, by Anpep in LLC-PK1 cells. Treatment of the cells with Anpep siRNA increased total cellular Na(+)-K(+)-ATPase activity and basolateral Na(+)-K(+)-ATPase abundance by approximately twofold. Conversely, Anpep overexpression reduced Na(+)-K(+)-ATPase activity and basolateral abundance by approximately 50%. Similar effects were observed after treatment with ANG IV (10 nM, x30 min and 12 h). ANG IV receptor (AGTRIV) knockdown via specific siRNA relieved the decreases in basolateral Na(+)-K(+)-ATPase levels and activity induced by Anpep overexpression. In sum, these results demonstrate that Anpep reduces basolateral Na(+)-K(+)-ATPase levels via ANG IV/AGTRIV signaling. This novel pathway may be important in renal adaptation to high salt.

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Angiotensinase activities in the kidney of renovascular hypertensive rats

Cited by 20 publications

References 32 publications

Effects of ACE inhibition on proximal tubule sodium transport

Effects of ACE inhibition on proximal tubule sodium transport

Role of central and peripheral aminopeptidase activities in the control of blood pressure: a working hypothesis

Aminopeptidase N reduces basolateral Na⁺-K⁺-ATPase in proximal tubule cells

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Angiotensinase activities in the kidney of renovascular hypertensive rats

Cited by 20 publications

References 32 publications

Effects of ACE inhibition on proximal tubule sodium transport

Effects of ACE inhibition on proximal tubule sodium transport

Role of central and peripheral aminopeptidase activities in the control of blood pressure: a working hypothesis

Aminopeptidase N reduces basolateral Na+-K+-ATPase in proximal tubule cells

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Product

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Aminopeptidase N reduces basolateral Na⁺-K⁺-ATPase in proximal tubule cells