Reduction in renal blood flow following administration of norepinephrine and phenylephrine in septic rats treated with Kir6.1 ATP-sensitive and KCa1.1 calcium-activated K+ channel blockers

Sant’Helena, Bruna da Rosa Maggi; Guarido, Karla Lorena; Souza, Priscila de; Crestani, Sandra; Silva-Santos, José Eduardo da

doi:10.1016/j.ejphar.2015.08.014

Cited by 5 publications

(1 citation statement)

References 34 publications

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“…During the experiments, the animals were maintained on a warming pad and allowed to breathe spontaneously. An interval of 20 min was observed before the measurement of basal values and renal blood flow was measured for an additional 15 min [18]. …”

Section: Methodsmentioning

confidence: 99%

Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development

Constantino

Galant

Vuolo

et al. 2017

ICMx

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BackgroundExtracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow.MethodsSepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated.ResultsAn increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow.ConclusionsECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult.

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Section: Methodsmentioning

confidence: 99%

Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development

Constantino

Galant

Vuolo

et al. 2017

ICMx

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Cardiac Surgery-Associated Acute Kidney Injury

Fischer¹,

Salaunkey

2017

Curr Anesthesiol Rep

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The role of nitric oxide in sepsis-associated kidney injury

Oliveira

Assreuy

2022

Bioscience Reports

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Sepsis is one of the leading causes of acute kidney injury (AKI), and several mechanisms including microcirculatory alterations, oxidative stress, and endothelial cell dysfunction are involved. Nitric oxide (NO) is one of the common elements to all these mechanisms. Although all three nitric oxide synthase (NOS) isoforms are constitutively expressed within the kidneys, they contribute in different ways to the nitrergic signaling. While the endothelial (eNOS) and neuronal (nNOS) isoforms are likely to be the main sources of NO under basal conditions and participates in the regulation of renal hemodynamics, the inducible isoform (iNOS) is dramatically increased in conditions such as sepsis. The overexpression of iNOS in the renal cortex causes a shunting of blood to this region, with consequent medullary ischemia in sepsis. Differences in the vascular reactivity among different vascular beds may also help to explain renal failure in this condition. While most of the vessels present vasoplegia and do not respond to vasoconstrictors, renal microcirculation behaves differently from nonrenal vascular beds, displaying similar constrictor responses in control and septic conditions. The selective inhibition of iNOS, without affecting other isoforms, has been described as the ideal scenario. However, iNOS is also constitutively expressed in the kidneys and the NO produced by this isoform is important for the immune defense. In this sense, instead of a direct iNOS inhibition, targeting the NO effectors such as guanylyl cyclase, potassium channels, peroxynitrite, and S-nitrosothiols, may be a more interesting approach in sepsis-AKI and further investigation is warranted.

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Reduction in renal blood flow following administration of norepinephrine and phenylephrine in septic rats treated with Kir6.1 ATP-sensitive and KCa1.1 calcium-activated K+ channel blockers

Cited by 5 publications

References 34 publications

Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development

Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development

Cardiac Surgery-Associated Acute Kidney Injury

The role of nitric oxide in sepsis-associated kidney injury

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