Contrast‐enhanced ultrasonography is a valid technique for the assessment of renal microvascular perfusion dysfunction in diabetic <scp>G</scp>oto‐<scp>K</scp>akizaki rats

Ma, Fang; Yadav, Ganga Prasad; Cang, Yan-qin; Dang, Yuanyuan; Wang, Chaoqing; Liu, Bo; Guo, Le‐Hang; Li, Xinhua; Peng, Ai

doi:10.1111/nep.12159

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…The underlying cause is most likely multifactorial, including the observed decreased L-arginine/ADMA ratio, which could lead to decreased NO-dependent vasodilatation. This is in line with the renal microvascular perfusion dysfunction seen in non-atherosclerotic diabetic rats [ 39 ]. Furthermore, we detected a lowered vascular density as measured by relative vessel area in the kidneys from ob/ob mice.…”

Section: Discussionsupporting

confidence: 82%

Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice

et al. 2015

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BackgroundType 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob) mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.Methods and ResultsIn this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.ConclusionIn parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

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Section: Discussionsupporting

confidence: 82%

Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice

et al. 2015

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“…Although the results of the present study do suggest that bulk hyperemic responses in GK are somewhat reduced, they did consistently exceed 85% of those in WKY, suggesting that bulk blood flow responses may not be the most significant concern with T2DM in GK rats. Rather, the consistent observation from multiple laboratories (36), and the present study, that there is a reduced skeletal muscle performance in GK rats may reflect altered hemodynamic control in the distal microcirculation impairing perfusiondemand matching. This would be consistent with the previous work from the Poole laboratory (11,43,44) as well as the recent studies from our group that demonstrated a progressive impairment to both microvascular perfusion distribution and system flexibility in terms of the temporal control over perfusion distribution across multiple models of elevated cardiovascular disease risk (Ref.…”

Section: Discussionsupporting

confidence: 73%

Type 2 diabetes mellitus in the Goto-Kakizaki rat impairs microvascular function and contributes to premature skeletal muscle fatigue

Frisbee

Lewis

Kasper

et al. 2019

Journal of Applied Physiology

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Despite extensive investigation into the impact of metabolic disease on vascular function and, by extension, tissue perfusion and organ function, interpreting results for specific risk factors can be complicated by the additional risks present in most models. To specifically determine the impact of type II diabetes without obesity on skeletal muscle microvascular structure/function, and on active hyperemia with elevated metabolic demand, we used 17‐week old Goto‐Kakizaki rats (GK) to study microvascular function at multiple levels of resolution. Gracilis muscle arterioles demonstrated blunted dilation to acetylcholine (both ex vivo proximal and in situ distal arterioles) and elevated shear (distal arterioles only). All other alterations to reactivity appeared to reflect compromised endothelial function associated with increased TxA2 production and oxidant stress/inflammation rather than alterations to vascular smooth muscle function. Structural changes to the microcirculation of GK were confined to reduced microvessel density of ~12%, with no evidence for altered vascular wall mechanics. Active hyperemia with either field stimulation of in situ cremaster muscle or electrical stimulation via the sciatic nerve for in situ gastrocnemius muscle was blunted in GK; primarily due to blunted functional dilation of skeletal muscle arterioles. The blunted active hyperemia was associated with impaired oxygen uptake (VO2) across the muscle and an accelerated muscle fatigue. Acute interventions to reduce oxidant stress (TEMPOL) and TxA2 action (SQ‐29548) or production (dazmegrel) improved muscle perfusion, VO2, and muscle performance. These results suggest that T2DM in GK impairs skeletal muscle arteriolar function apparently early in the progression of the disease and potentially via an increased ROS/inflammation‐induced TxA2 production/action on network function as a major contributing mechanism. Support or Funding Information American Heart Association and National Institutes of Health (USA); Canadian Institutes for Health Research and Natural Sciences and Engineering Research Council (Canada) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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“…In diabetic Goto-Kakizaki rats, renal perfusion, as estimated by CEUS, consistently matched the pathological changes in the kidneys [24] . When compared to normal controls, dogs with iatrogenic hypercortisolism had significantly increased CEUS PI and AUC values in their kidneys compared to controls [25] .…”

Section: Renal Microvascular Perfusion Evaluation In Animal Modelsmentioning

confidence: 84%

Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation

Mohan

2016

Journal of Translational Internal Medicine

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This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, noninvasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease.

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Contrast‐enhanced ultrasonography is a valid technique for the assessment of renal microvascular perfusion dysfunction in diabetic Goto‐Kakizaki rats

Abstract: Contrast-enhanced ultrasonography is a valid technique for the real-time and dynamic assessment of renal cortex microvascular perfusion and haemodynamic characterization in GK rats.

Cited by 7 publications

References 22 publications

Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice

Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice

Type 2 diabetes mellitus in the Goto-Kakizaki rat impairs microvascular function and contributes to premature skeletal muscle fatigue

Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation

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