TNFR1-deficient mice display altered blood pressure and renal responses to ANG II infusion

Chen, Chun Cheng Andy; Pedraza, Paulina L.; Hao, Shoujin; Stier, Charles T.; Ferreri, Nicholas R.

doi:10.1152/ajprenal.00344.2010

Cited by 41 publications

(44 citation statements)

References 49 publications

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“…Chen et al (7) reported that basal MAP in conscious TNF␣R1 KO mice was not significantly different from that in WT mice. However, the results of the present study, which was conducted in anesthetized mice, demonstrate that basal MAP was lower in TNF␣R1 KO than WT mice.…”

Section: Discussionmentioning

confidence: 96%

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Tumor necrosis factor-α receptor type 1, not type 2, mediates its acute responses in the kidney

Castillo

Islam

Prieto

et al. 2012

American Journal of Physiology-Renal Physiology

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Acute administration of tumor necrosis factor-α (TNF-α) resulted in decreases in renal blood flow (RBF) and glomerular filtration rate (GFR) but induced diuretic and natriuretic responses in mice. To define the receptor subtypes involved in these renal responses, experiments were conducted to assess the responses to human recombinant TNF-α (0.3 ng·min−1·g body wt−1iv infusion for 75 min) in gene knockout (KO) mice for TNF-α receptor type 1 (TNFαR1 KO, n = 5) or type 2 (TNFαR2 KO, n = 6), and the results were compared with those obtained in corresponding wild-type [WT (C57BL/6), n = 6] mice. Basal levels of RBF (PAH clearance) and GFR (inulin clearance) were similar in TNFαR1 KO, but were lower in TNFαR2 KO, than WT mice. TNF-α infusion in WT mice decreased RBF and GFR but caused a natriuretic response, as reported previously. In TNFαR1 KO mice, TNF-α infusion failed to cause such vasoconstrictor or natriuretic responses; rather, there was an increase in RBF and a decrease in renal vascular resistance. Similar responses were also observed with infusion of murine recombinant TNF-α in TNFαR1 KO mice ( n = 5). However, TNF-α infusion in TNFαR2 KO mice caused changes in renal parameters qualitatively similar to those observed in WT mice. Immunohistochemical analysis in kidney slices from WT mice demonstrated that while both receptor types were generally located in the renal vascular and tubular cells, only TNFαR1 was located in vascular smooth muscle cells. There was an increase in TNFαR1 immunoreactivity in TNFαR2 KO mice, and vice versa, compared with WT mice. Collectively, these functional and immunohistological findings in the present study demonstrate that the activation of TNFαR1, not TNFαR2, is mainly involved in mediating the acute renal vasoconstrictor and natriuretic actions of TNF-α.

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Section: Discussionmentioning

confidence: 96%

“…This form of human recombinant TNF-␣ was widely used in other earlier in vivo studies (7,29,32,33) conducted in mice. The specificity of human TNF-␣ action in the mice was demonstrated in our earlier study (32).…”

mentioning

confidence: 99%

Tumor necrosis factor-α receptor type 1, not type 2, mediates its acute responses in the kidney

Castillo

Islam

Prieto

et al. 2012

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…These results are in stark contrast to those shown in TNF-␣ KO mice (131) where the increase in blood pressure induced by infusion of 1 g·kg Ϫ1 ·min Ϫ1 ANG II was blunted compared with WT mice and to those shown by Guzik et al (51) where etanercept reduced the increase in blood pressure induced by infusion of ANG II at a rate of 490 ng·kg Ϫ1 ·min Ϫ . While the explanation is not clear, it could be due to the different doses of ANG II used (and hence possibly different mechanisms leading to hypertension), due to the background of the mice (C57Bc/6J vs. B6129SF2/J), or because infusion of ANG II in TNFR1 KO mice increases both TNF-␣ and TNFR2 (24). This later point raises the possibility that the observed phenotype is the result of hyperactive TNFR2 as opposed to a lack of TNFR1 and TNFR2 has been shown to mediate renal macrophage infiltration, glomerulosclerosis, and interstitial fibrosis in ANG II-induced hypertension (129).…”

mentioning

confidence: 99%

Tumor necrosis factor-α: regulation of renal function and blood pressure

Ramseyer

Garvin

2013

American Journal of Physiology-Renal Physiology

149

106

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“…Other studies using TNFR1‐KO mice described an even greater hypertensive response to Ang‐II infusion than WT mice (Chen et al. 2010), or no difference between TNFR1‐KO and WT mice (Singh et al. 2013).…”

Section: Discussionmentioning

confidence: 99%

TNF/Ang-II synergy is obligate for fibroinflammatory pathology, but not for changes in cardiorenal function

et al. 2016

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Angiotensin‐II (Ang‐II) infusion is associated with the development of interstitial fibrosis in both heart and kidney as a result of chemokine‐dependent uptake of monocytes and subsequent development of myeloid fibroblasts. This study emphasizes on the synergistic role of tumor necrosis factor (TNF) on the time course of Ang‐II‐induced fibrosis and inflammation in heart and kidney. In wild‐type (WT) hearts, Ang‐II‐induced fibrosis peaked within 1 week of infusion and remained stable over a 6‐week period, while the myeloid fibroblasts disappeared; TNF receptor‐1‐knockout (TNFR1‐KO) hearts did not develop a myeloid response or cardiac fibrosis during this time. WT hearts developed more accelerated cardiac hypertrophy and remodeling than TNFR1‐KO. In the kidney, 1‐week Ang‐II infusion did not evoke a fibrotic response; however, after 6 weeks, WT kidneys displayed modest but significant tubulointerstitial collagen deposition associated with the appearance of myeloid cells and profibrotic gene activation. Renal fibrosis was not seen in Ang‐II‐infused TNFR1‐KO. By contrast, while hypertension increased and cardiac function decreased more slowly in TNFR1‐KO than WT, they were equivalently abnormal at 6 weeks. Similarly, serum markers for renal dysfunction were not different after 6 weeks. In conclusion, Ang‐II infusion initiated fibroinflammatory responses with different time courses in heart and kidney, both requiring TNFR1 signaling, and both associated with monocyte‐derived myeloid fibroblasts. TNFR1 deletion obviated the fibroinflammatory effects of Ang‐II, but did not alter changes in blood pressure and cardiorenal function after 6 weeks. Thus, the synergy of TNF with Ang‐II targets the fibroinflammatory component of Ang‐II signaling.

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TNFR1-deficient mice display altered blood pressure and renal responses to ANG II infusion

Cited by 41 publications

References 49 publications

Tumor necrosis factor-α receptor type 1, not type 2, mediates its acute responses in the kidney

Tumor necrosis factor-α receptor type 1, not type 2, mediates its acute responses in the kidney

Tumor necrosis factor-α: regulation of renal function and blood pressure

TNF/Ang-II synergy is obligate for fibroinflammatory pathology, but not for changes in cardiorenal function

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