The intrarenal renin-angiotensin system: does it exist? Implications from a recent study in renal angiotensin-converting enzyme knockout mice

Lu, Xifeng; Roksnoer, Lodi C.W.; Danser, A.H. Jan

doi:10.1093/ndt/gft333

Cited by 14 publications

(15 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been hypothesized that one of the protective factors could be mast cell chymase [30]. Even better established is the role of chymase as an alternative angiotensin convertase; locally generated angiotensin may increase proteinuria as well as systemic blood pressure [31]. Our results suggest that chymase is generated in lupus nephritis, yet its influence on renal function is weaker than in other renal disease, such as diabetic nephropathy [11].…”

Section: Discussionmentioning

confidence: 75%

Renal interstitial mast cell counts differ across classes of proliferative lupus nephritis

Kaczmarczyk

Kosałka

Soja

et al. 2014

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Systemic lupus erythematosus frequently involves the kidneys leading to significant morbidity and mortality. It is classified according to glomerular involvement pattern but tubulointerstitial lesions are also important for progression and prognosis, as seen in other kidney glomerular diseases. One of the cell types which participate in this process are mast cells. The aim of the study was to analyze the counts of tryptase-positive and chymase-positive mast cells in lupus nephritis classes II, III and IV. Material consisted of 42 renal biopsies from patients with lupus nephritis; 11 class II, 9 class III and 22 class IV. Chymase-and tryptase-containing cells were stained by immunohistochemistry and counted microscopically. Mean count of chymase-positive mast cells was 9.8/10 high power fields (hpf) for the whole group, 4.66 for class II, 11.89 for class III, and 11.51 for class IV. The mean count of tryptase-positive cells was 18.6/10 hpf for the whole group, 7.65 for class II, 25.57 for class III, and 21.23 for class IV. The differences between lupus nephritis classes were significant both for chymase-and tryptase-positive cells. Tryptase-but not chymase-positive cell counts showed a correlation with the creatinine level (R = 0.35). These results suggest that mast cells are involved to a different degree in the pathogenesis of lupus nephritis depending on the class of the disease.

show abstract

Section: Discussionmentioning

confidence: 75%

Renal interstitial mast cell counts differ across classes of proliferative lupus nephritis

Kaczmarczyk

Kosałka

Soja

et al. 2014

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

show abstract

“…In this context, the observed antiproliferative effects of ARBs are basically a reflection of AT1-mediated signaling in cancer cells. This approach does not take into account the possible role of locally produced AngII, which has been demonstrated to be of major importance in other cell types (Reid et al, 2011;Angeli et al, 2013;Lu et al, 2013). In addition, this approach also ignores the possibility of ARBinduced AngII-independent effects which have been demonstrated in other cell types (Alhusban et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Another important consideration in investigating the effects of ARBs is the concomitant treatment with exogenous AngII (Uemura et al, 2003;Kosaka et al, 2007;Chen et al, 2013), which only blunted AngII-mediated effects. This paradigm ignores AngII-independent effects of candesartan as well as the role of locally produced AngII, which has been well characterized in a variety of tissues and cell types (Reid et al, 2011;Angeli et al, 2013;Lu et al, 2013). Recently, candesartan was shown to be proangiogenic in cerebral microvascular endothelial cells via activation of the angiotensin II type 2 (AT2) receptor (Alhusban et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Clinically Relevant Doses of Candesartan Inhibit Growth of Prostate Tumor Xenografts In Vivo through Modulation of Tumor Angiogenesis

Alhusban

Al-Azayzih

Goc

et al. 2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Angiotensin II receptor type 1 blockers (ARBs), widely used antihypertensive drugs, have also been investigated for their anticancer effects. The effect of ARBs on prostate cancer in experimental models compared with meta-analysis data from clinical trials is conflicting. Whereas this discrepancy might be due to the use of supratherapeutic doses of ARBs in cellular and animal models as compared with the clinical doses used in human trials, further investigation of the effects of clinical doses of ARBs on prostate cancer in experimental models is warranted. In the current study, we sought to determine the effects of candesartan on prostate cancer cellular function in vitro and tumor growth in vivo, and characterize the underlying mechanisms. Our analysis indicated that clinically relevant doses of candesartan significantly inhibited growth of PC3 cell tumor xenografts in mice.Interestingly, the same concentrations of candesartan actually promoted prostate cancer cellular function in vitro, through a modest but significant inhibition in apoptosis. Inhibition of tumor growth by candesartan was associated with a decrease in vascular endothelial growth factor (VEGF) expression in tumors and inhibition of tumor angiogenesis, but normalization of tumor vasculature. Although candesartan did not impair PC3 cell viability, it inhibited endothelialbarrier disruption by tumor-derived factors. Furthermore, candesartan significantly inhibited expression of VEGF in PC3 and DU145 cell lines independent of angiotensin II type 2 receptor, but potentially via angiotensin II type 1 receptor inhibition. Our findings clearly demonstrate the therapeutic potential of candesartan for prostate cancer and establish a link between ARBs, VEGF expression, and prostate tumor angiogenesis.

show abstract

“…[14][15][16][17] Physiologically, intrarenal RAS regulates the glomerular filtration rate, 18 blood pressure, and proximal tubular reabsorption. 19 Brain RAS modulates drinking behavior 20 and blood pressure.…”

mentioning

confidence: 99%

Renal denervation has blood pressure–independent protective effects on kidney and heart in a rat model of chronic kidney disease

Eriguchi

Tsuruya

Haruyama

et al. 2015

Kidney International

View full text Add to dashboard Cite

We elucidate the underlying mechanisms of bidirectional cardiorenal interaction, focusing on the sympathetic nerve driving disruption of the local renin-angiotensin system (RAS). A rat model of N(ω)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) administration was used to induce damage in the heart and kidney, similar to cardiorenal syndrome. L-NAME induced sympathetic nerve-RAS overactivity and cardiorenal injury accompanied by local RAS elevations. These were suppressed by bilateral renal denervation, but not by hydralazine treatment, despite the blood pressure being kept the same between the two groups. Although L-NAME induced angiotensinogen (AGT) protein augmentation in both organs, AGT mRNA decreased in the kidney and increased in the heart in a contradictory manner. Immunostaining for AGT suggested that renal denervation suppressed AGT onsite generation from activated resident macrophages of the heart and circulating AGT excretion from glomeruli of the kidney. We also examined rats treated with L-NAME plus unilateral denervation to confirm direct sympathetic regulation of intrarenal RAS. The levels of urinary AGT and renal angiotensin II content and the degrees of renal injury from denervated kidneys were less than those from contralateral innervated kidneys within the same rats. Thus, renal denervation has blood pressure-independent beneficial effects associated with local RAS inhibition.

show abstract

The intrarenal renin-angiotensin system: does it exist? Implications from a recent study in renal angiotensin-converting enzyme knockout mice

Cited by 14 publications

References 33 publications

Renal interstitial mast cell counts differ across classes of proliferative lupus nephritis

Renal interstitial mast cell counts differ across classes of proliferative lupus nephritis

Clinically Relevant Doses of Candesartan Inhibit Growth of Prostate Tumor Xenografts In Vivo through Modulation of Tumor Angiogenesis

Renal denervation has blood pressure–independent protective effects on kidney and heart in a rat model of chronic kidney disease

Contact Info

Product

Resources

About