Nitrite-mediated renal vasodilatation is increased during ischemic conditions via cGMP-independent signaling
Abstract
The kidney is vulnerable to hypoxia, and substantial efforts have been made to ameliorate renal ischemic injury secondary to pathological conditions. Stimulation of the nitrate-nitrite-nitric oxide pathway is associated with renal and cardiovascular protection in disease models, but less is known about the vascular effects during renal ischemia. This study was aimed at investigating the vascular effects of nitrite in the kidney during normoxic and ischemic conditions. Using a multiwire myograph system, we assessed nitrite-mediated relaxation (10(-9)-10(-4)mol/L) in isolated and preconstricted renal interlobar arteries from C57BL/6 mice under normal conditions (pO2 13kPa; pH 7.4) and with low oxygen tension and low pH to mimic ischemia (pO2 3kPa; pH 6.6). Xanthine oxidoreductase expression was analyzed by quantitative PCR, and production of reactive nitrogen species was measured by DAF-FM DA fluorescence. During normoxia significant vasodilatation (15±3%) was observed only at the highest concentration of nitrite, which was dependent on NO-sGC-cGMP signaling. The vasodilatory responses to nitrite were greatly sensitized and enhanced during hypoxia with low pH, demonstrating significant dilatation (11±1%) already in the physiological range (10(-8)mol/L), with a maximum response of 27±2% at 10(-4) mol/L. In contrast to normoxia, and to that observed with a classical NO donor (DEA NONOate), this sensitization was independent of sGC-cGMP signaling. Moreover, inhibition of various e…
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There exists a broad range of redox-derived nitrogen oxides that exert both cGMP-dependent and -independent signaling actions as a result of nitrosative-, nitrative- and oxidative-induced post-translational protein modifications and subsequent changes in protein function and gene expression profiles.
“There exists a broad range of redox-derived nitrogen oxides that exert both cGMP-dependent and -independent signaling actions as a result of nitrosative-, nitrative- and oxidative-induced post-translational protein modifications and subsequent changes in protein function and gene expression profiles[100–102].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [101]
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- Authors
- Liu, M., Zollbrecht, C., Peleli, M., Lundberg, J. O., Weitzberg, E., & Carlström, M.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Carlström, Mattias
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 84
- Pages
- 154-160
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2088922255
- Cited by
- 30
- References
- 34
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 1
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- the Swedish Research Council (521–2011–2639)
- the Swedish Heart and Lung Foundation (20140448, 20110589)
- the Jeanssons Foundation (JS2013–00064)
- the Karolinska Institutet. E.W. and J.O.L. are codirectors of Heartbeet Ltd
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- nitrite, renal vasodilation, renal ischemia, hypoxia, acidosis, xanthine oxidoreductase, nitrate-nitrite-nitric oxide pathway, renal interlobar arteries, vasorelaxation, reactive nitrogen species, febuxostat, allopurinol
- MeSH terms
- Animals, Cyclic GMP, Ischemia, Kidney, Male, Mice, Inbred C57BL, Nitrites, Vasodilation, Xanthine Oxidase, Second Messenger Systems, Cell Hypoxia
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