Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition

Granstam, Sven-Olof

doi:10.1007/s12576-011-0171-x

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…We do not know the exact cause for these observations, and can only speculate that it may be a consequence of pump malfunction, or a delayed response to the adenosine. In a previous study, Granstam and Granstam reported a 60% decrease in blood flow at similar dose using microsphere analysis following the L‐NAME injection (dose), which was a larger change than we have observed. However, they have followed the bolus L‐NAME injection with an infusion for 10 min at a rate of 10 mg/kg.…”

Section: Discussioncontrasting

confidence: 46%

Sensitivity of arterial spin labeling perfusion MRI to pharmacologically induced perfusion changes in rat kidneys

Tan

Thacker

Franklin

et al. 2014

Magnetic Resonance Imaging

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Purpose To investigate whether arterial spin labeling (ASL) MRI is sensitive to changes by pharmacologically induced vasodilation and vasoconstriction in rat kidneys. Materials and Methods Changes in renal cortical blood flow in seven rats were induced by Adenosine infusion (vasodilation) and L-NAME injection (vasoconstriction). All imaging studies were performed on a 3T scanner using a FAIR-TrueFISP sequence for the ASL implementation. The acquisition length for each ASL scan was 6 minutes. Cortical perfusion rates were calculated using regions-of-interest analysis, and the differences in perfusion rates during baseline, vasodilation, and vasoconstriction were compared and assessed for statistical significance. Results Compared to the baseline, an average of 94 mL/100g/min increase and 157 mL/100g/min decrease in cortical perfusion was observed following adenosine infusion and L-NAME administration respectively. The changes in cortical perfusion were significant between baseline and vasodilation (p < 0.05), baseline and vasoconstriction (p < 0.01), and vasodilation and vasoconstriction (p < 0.01). Conclusion ASL is sensitive to pharmacologically induced perfusion changes in rat kidneys at doses comparable to current use. The preliminary results suggest the feasibility of ASL for investigating renal blood flow in a variety of rodent models.

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Section: Discussioncontrasting

confidence: 46%

Sensitivity of arterial spin labeling perfusion MRI to pharmacologically induced perfusion changes in rat kidneys

Tan

Thacker

Franklin

et al. 2014

Magnetic Resonance Imaging

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“…For L‐NAME, the dosage of 25 mg/kg caused a decrease of 55% in RBP 40 min after L‐NAME delivery (Figure 7A). The ~ 55% change is similar to the change of ~ 60% with the same dose reported in Granstam and Granstam 58 . As shown in Figure 7, the pharmacological agent‐induced RBP changes measured by FAIR ASL are similar to the RBF changes induced by the same agents with the same delivery protocol measured by the invasive flow probe method.…”

Section: Discussionsupporting

confidence: 78%

Robust arterial spin labeling MRI measurement of pharmacologically induced perfusion change in rat kidneys

et al. 2021

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Kidney diseases such as acute kidney injury, diabetic nephropathy and chronic kidney disease (CKD) are related to dysfunctions of the microvasculature in the kidney causing a decrease in renal blood perfusion (RBP). Pharmacological intervention to improve the function of the microvasculature is a viable strategy for the potential treatment of these diseases. The measurement of RBP is a reliable biomarker to evaluate the efficacy of pharmacological agents' actions on the microvasculature, and measurement of RBP responses to different pharmacological agents can also help elucidate the mechanism of hemodynamic regulation in the kidney. Magnetic resonance imaging (MRI) with flow‐sensitive alternating inversion recovery (FAIR) arterial spin labeling (ASL) has been used to measure RBP in humans and animals. However, artifacts caused by respiratory and peristaltic motions limit the potential of FAIR ASL in drug discovery and kidney research. In this study, the combined anesthesia protocol of inactin with a low dose of isoflurane was used to fully suppress peristalsis in rats, which were ventilated with an MRI‐synchronized ventilator. FAIR ASL data were acquired in eight axial slices using a single‐shot, gradient‐echo, echo‐planar imaging (EPI) sequence. The artifacts in the FAIR ASL RBP measurement due to respiratory and peristaltic motions were substantially eliminated. The RBP responses to fenoldopam and L‐NAME were measured, and the increase and decrease in RBP caused by fenoldopam and L‐NAME, respectively, were robustly observed. To further validate FAIR ASL, the renal blood flow (RBF) responses to the same agents were measured by an invasive perivascular flow probe method. The pharmacological agent‐induced responses in RBP and RBF are similar. This indicates that FAIR ASL has the sensitivity to measure pharmacologically induced changes in RBP. FAIR ASL with multislice EPI can be a valuable tool for supporting drug discovery, and for elucidating the mechanism of hemodynamic regulation in kidneys.

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“…In the study by Granstam et al , diabetic rats exhibited decrease renal blood flow as compared with non-diabetic rats, providing evidence of vasoconstriction in the context of diabetes. Treatment of diabetic rats with the ET A receptor antagonist BQ-123 implied no alteration in renal blood flow [ 72 ]. However, in isolated glomeruli from diabetic rats albumin permeability was increased, while treatment with BQ-123 significantly reduced the albumin permeability in a dose-dependent manner [ 37 ].…”

Section: Endothelin Antagonists In Diabetic Nephropathymentioning

confidence: 99%

Endothelin Blockade in Diabetic Kidney Disease

Anguiano

Riera

Pascual

et al. 2015

JCM

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Diabetic kidney disease (DKD) remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1) has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ETA) receptor. Therefore, endothelin receptor antagonists have been proposed as potential drug targets. In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. Currently, its renoprotective effect in a long-time clinical trial is being tested. This review focuses on the localization of endothelin receptors (ETA and ETB) within the kidney, as well as the ET-1 functions through them. In addition, we summarize the therapeutic benefit of endothelin receptor antagonists in experimental and human studies and the adverse effects that have been described.

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Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition

Cited by 8 publications

References 37 publications

Sensitivity of arterial spin labeling perfusion MRI to pharmacologically induced perfusion changes in rat kidneys

Sensitivity of arterial spin labeling perfusion MRI to pharmacologically induced perfusion changes in rat kidneys

Robust arterial spin labeling MRI measurement of pharmacologically induced perfusion change in rat kidneys

Endothelin Blockade in Diabetic Kidney Disease

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