Role of Interstitial ATP and Adenosine in the Regulation of Renal Hemodynamics and Microvascular Function

Nishiyama, Akira; Rahman, Matlubur; Inscho, Edward W.

doi:10.1291/hypres.27.791

Cited by 52 publications

(52 citation statements)

References 121 publications

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“…One often-underappreciated function of interstitial fibroblasts is their involvement in regulation of renal hemodynamics and microvascular function through generation of extracellular adenosine (63,64). To maintain glomerular filtration within a narrow range, the kidney responds to increased intratubular NaCl levels (upon increased GFR) by vasoconstriction of afferent arterioles (to decrease GFR) (65).…”

Section: Adenosinementioning

confidence: 99%

“…One enzyme that catalyzes hydrolysis of ATP to adenosine is 59ectonucleotidase (59NT, CD73), which is expressed in the kidney predominantly by resident fibroblasts (a characteristic that has made it a popular marker for renal fibroblasts) (63). 59NT-deficient mice display substantial reduction of extracellular adenosine levels and reduced kidney weight; however, renal blood flow and GFR are unaltered (67), possibly because of intrinsic activity of interstitial ATP on vascular tone (64). In the chronically injured kidney, 59NT-positive fibroblasts and extracellular adenosine levels accumulate, possibly contributing to the lowered GFR through afferent arteriole constriction, which is typical of CKD (2).…”

Section: Adenosinementioning

confidence: 99%

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Physiology of the Renal Interstitium

Zeisberg

Kalluri

2015

Clinical Journal of the American Society of Nephrology

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Long overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated with function. With identification of interstitial reninand erythropoietin-producing cells, the most prominent endocrine functions of the kidney have now been attributed to the renal interstitium. This article reviews the functional role of renal interstitium.

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Section: Adenosinementioning

confidence: 99%

Section: Adenosinementioning

confidence: 99%

Physiology of the Renal Interstitium

Zeisberg

Kalluri

2015

Clinical Journal of the American Society of Nephrology

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“…Interestingly, catecholamine, angiotensin, aldosterone, and cytokines are known to be involved in the pathophysiology of CHF (2)(3)(4)(5), as evidenced by the fact that β-adrenoceptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, and aldosterone receptor antagonists are widely accepted as drugs for CHF (6,7). Adenosine has biological effects on various tissues (8)(9)(10). Since several lines of evidence (9,10) support the idea that adenosine is cardioprotective against deleterious sequels in CHF as well as ischemic heart disease, it is intriguing and important to analyze the adenosine receptor-or adenosine metabolismrelated genes using DNA microarray analysis.…”

Section: Introductionmentioning

confidence: 99%

Impact of Adenosine Receptor Signaling and Metabolism on Pathophysiology in Patients with Chronic Heart Failure

et al. 2007

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Adenosine is well known to be a cardioprotective substance in ischemic heart disease. However, the modulation of adenosine receptors and the production and degradation of endogenous adenosine in chronic heart failure (CHF) are not fully understood. We analyzed the gene expression patterns of adenosine-related genes in human failing and nonfailing myocardium using DNA microarray analysis and quantitative real

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“…ATP has been shown to regulate renal blood flow, glomerular filtration rate, water and salt reabsorption and tubuloglomerular feedback [1,7,10,11] .…”

Section: Introductionmentioning

confidence: 99%

Adenosine 5′-triphosphate stimulates the increase of TGF-β1 in rat mesangial cells under high-glucose conditions via reactive oxygen species and ERK1/2

Xue

Yuan

et al. 2009

Acta Pharmacol Sin

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Aim: To investigate the role of adenosine 5′-triphosphate (ATP)-induced generation of reactive oxygen species (ROS) and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the production of transforming growth factor-β1 (TGF-β1) in cultured rat glomerular mesangial cells under high-glucose conditions. Methods: Subconfluent glomerular mesangial cells were serum-starved for 24 h and pretreated with suramin, diphenylenechloride iodonium (DPI) or PD98059 followed by stimulation with a high concentration of glucose (30 mmol/L D-glucose) or ATP (300 μmol/L). Extracellular and total ATP and ROS production were detected using commercially available kits. Phosphorylation of ERK1/2 was evaluated by Western blot. TGF-β1 mRNA expression was examined by real-time PCR. Results: Suramin had a dose-dependent inhibitory effect on the generation of ROS induced by high glucose. Extracellular ATP production by mesangial cells increased markedly after a 2-h incubation with high glucose. ROS production was upregulated in mesangial cells after 5 min incubation with 300 μmol/L ATP and was sustained for 120 min. ERK1/2 was significantly activated after 5 min incubation of mesangial cells with ATP, this activation was partially inhibited by DPI. The effects of high glucose on TGF-β1 mRNA were markedly inhibited by suramin, DPI or PD98059. Conclusion: Our results suggest that a high concentration of glucose increases the extracellular levels of ATP in mesangial cells within a short time-frame. ATP, in turn, activates ERK1/2, an effect which is at least partially dependent on ROS, which results in the upregulation of TGF-β1.

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Role of Interstitial ATP and Adenosine in the Regulation of Renal Hemodynamics and Microvascular Function

Cited by 52 publications

References 121 publications

Physiology of the Renal Interstitium

Physiology of the Renal Interstitium

Impact of Adenosine Receptor Signaling and Metabolism on Pathophysiology in Patients with Chronic Heart Failure

Adenosine 5′-triphosphate stimulates the increase of TGF-β1 in rat mesangial cells under high-glucose conditions via reactive oxygen species and ERK1/2

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