A Forgotten Method to Induce Experimental Chronic Renal Failure in the Rat by Ligation of the Renal Parenchyma

Pérez-Ruiz, L; Ros-López, S; Cardús, Anna; Fernàndez, Elvira; Valdivielso, José M.

doi:10.1159/000092198

Cited by 19 publications

(10 citation statements)

References 15 publications

(8 reference statements)

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“…Sprague‐Dawley rats (200–225 g) were anesthetized with isoflurane, and right nephrectomy was performed. After 1 wk, animals suffered two‐thirds nephrectomy in the left kidney by ligation of both poles as previously described (22) . Animals with five‐sixths nephrectomy were divided into three groups.…”

Section: Methodsmentioning

confidence: 99%

Differential Effects of Vitamin D Analogs on Vascular Calcification

Cardús

Panizo

Parisi

et al. 2007

Journal of Bone and Mineral Research

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153

118

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We tested the effects of calcitriol and its analog paricalcitol on VSMC calcification in vitro and in vivo. For that reason, cells and animals with five-sixths nephrectomy were treated with both compounds. Calcitriol, but not paricalcitol, increased VSMC calcification in vitro and in vivo independently of calcium and phosphate levels. This increase in calcification was parallel to an increase in the RANKL/OPG ratio.Introduction: Vascular calcification is a common finding in patients with endstage renal disease. Furthermore, those patients often present secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Thus, one of the main therapeutic options is to treat those patients with calcitriol or analogs. However, this treatment presents unwanted side effects, such as increases in vascular calcification. Materials and Methods: We tested the effect on vascular smooth muscle cell (VSMC) calcification of calcitriol and one of its analogs, paricalcitol, in vitro and in vivo in animals with endstage renal disease. Results: Calcitriol increased calcification of VSMCs cultured in calcification media. This effect was not present when cells were incubated with paricalcitol. Furthermore, only cells incubated with calcitriol showed an increased RANKL/ osteoprotegerin (OPG) expression. Animals with renal failure treated with hypercalcemic doses of calcitriol and paricalcitol showed an increase in systolic blood pressure. However, diastolic blood pressure only raised significantly in those animals treated with paricalcitol. This effect led to a significant increase in pulse pressure in animals treated with calcitriol. The increase in pulse pressure was likely caused by the extensive calcification observed in arteries of animals treated with calcitriol. This increase in calcification was not seen in arteries of animals treated with paricalcitol, despite having similar levels of serum calcium and phosphorus as animals treated with calcitriol. Furthermore, the decreases in serum PTH levels were similar in both treatments. Conclusions: We conclude that paricalcitol has a different effect than calcitriol in VSMC calcification and that this could explain part of the differences observed in the clinical settings.

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Section: Methodsmentioning

confidence: 99%

Differential Effects of Vitamin D Analogs on Vascular Calcification

Cardús

Panizo

Parisi

et al. 2007

Journal of Bone and Mineral Research

Self Cite

153

118

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“…Sprague-Dawley rats (200 to 225 g) underwent 5/6 nephrectomy by previously described procedures 19 and were divided in 2 groups. One group received calcitriol (1 g/kg 3 times a week for 8 weeks; nϭ9), whereas the second group received a vehicle injection (nϭ9).…”

Section: Experimental Animalsmentioning

confidence: 99%

RANKL Increases Vascular Smooth Muscle Cell Calcification Through a RANK-BMP4–Dependent Pathway

Panizo¹,

Cardús²,

Encinas³

et al. 2009

Circulation Research

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219

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Abstract-Vascular calcification commonly associated with several pathologies and it has been suggested to be similar to bone mineralization. The axis RANKL-OPG (receptor activator of nuclear factor B ligand-osteoprotegerin) finely controls bone turnover. RANKL has been suggested to increase vascular calcification, but direct evidence is missing. Thus, in the present work, we assess the effect of RANKL in vascular smooth muscle cell (VSMC) calcification. VSMCs incubated with RANKL showed a dose-dependent increase in calcification, which was abolished by coincubation with OPG. To test whether the effect was mediated by signaling to its receptor, knockdown of RANK was accomplished by short hairpin (sh)RNA. Indeed, cells lacking RANK showed no increases in vascular calcification when incubated with RANKL. To further elucidate the mechanism by which RANK activation increases calcification, we blocked both nuclear factor (NF)-B activation pathways. Only IKK␣ inactivation inhibited calcification, pointing to an involvement of the alternative NF-B activation pathway. Furthermore, RANKL addition increased bone morphogenetic protein (BMP)4 expression in VSMCs, and that increase disappeared in cells lacking RANK or IKK␣. The increase in calcification was also blunted by Noggin, pointing to a mediation of BMP4 in the calcification induced by RANKL. Furthermore, in an in vivo model, the increase in vascular calcium content was parallel to an increase in RANKL and BMP4 expression, which was localized in calcified areas. However, blood levels of the ratio RANKL/OPG did not change. We conclude that RANKL increases vascular smooth muscle cell calcification by binding to RANK and increasing BMP4 production through activation of the alternative NF-B pathway.

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“…Numbers per group were limited for logistical reasons due to total study size. The supplier performed surgery to nephrectomize rats using a staged surgical procedure similar to that described by Perez Ruiz et al (14). The rats' body weights were from 150 to 175 g when the supplier began surgery or when rats were allocated to the study.…”

Section: Animalsmentioning

confidence: 99%