Morphological Changes and Alterations in Regional Intrarenal Blood Flow Induced by Graded Renal Ischemia

Moran, K. T.; Mulhall, Joseph; Kelly, D. G.; Sheehan, S.; Dowsett, Julie; Dervan, P.; Fitzpatrick, John M.

doi:10.1016/s0022-5347(17)36629-6

Cited by 44 publications

(25 citation statements)

References 15 publications

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“…For example, CN inhibitor therapy has been linked to the development of FSGS in some patients, perhaps by promoting renal ischemia (29,65). In support of this hypothesis, glomerular volume was reduced in GqQ>L mice treated with FK506 (Table 3), consistent with the idea that FK506 caused renal ischemia and, in turn, a reduction in glomerular volume (66). Moreover, FK506 had little effect on GqQ>L-dependent induction of COX2 ( Figure 6J).…”

Section: Discussionsupporting

confidence: 65%

Gq signaling causes glomerular injury by activating TRPC6

Wang¹,

Jirka²,

Rosenberg³

et al. 2015

J. Clin. Invest.

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Section: Discussionsupporting

confidence: 65%

Gq signaling causes glomerular injury by activating TRPC6

Wang¹,

Jirka²,

Rosenberg³

et al. 2015

J. Clin. Invest.

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“…Glomeruli are easily identified by their round shape and by the fact that they are separated from the surrounding parenchyma by the capsular space of Bowman. Because the size and shape of glomeruli changes significantly in some glomerular diseases, [35][36][37][38] OCT may serve as a useful tool to detect such diseases. With its ability to image through a catheter or needle, OCT also has the potential of imaging glomeruli deeper in the kidney in addition to the superficial glomeruli.…”

Section: Discussionmentioning

confidence: 99%

High-resolution optical coherence tomography imaging of the living kidney

Andrews

Chen

Onozato

et al. 2008

Laboratory Investigation

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Optical coherence tomography (OCT) is a rapidly emerging imaging modality that can provide non-invasive, crosssectional, high-resolution images of tissue morphology in situ and in real-time. In the present series of studies, we used a high-speed OCT imaging system equipped with a frequency-swept laser light source (1.3 mm wavelength) to study living kidneys in situ. Adult, male Munich-Wistar rats were anesthetized, a laparotomy was performed and the living kidneys were exposed for in situ observation. We observed the kidneys prior to, during and following exposure to renal ischemia induced by clamping the renal artery. The effects of intravenous mannitol infusion (1.0 ml of 25%) prior to and during renal ischemia were also studied. Finally, living kidneys were flushed with a renal preservation solution, excised and observed while being stored at 0-41C. Three-dimensional OCT data sets enabled visualization of the morphology of the uriniferous tubules and the renal corpuscles. When renal ischemia was induced, OCT revealed dramatic shrinkage of tubular lumens due to swelling of the lining epithelium. Three-dimensional visualization and volumetric rendering software provided an accurate evaluation of volumetric changes in tubular lumens in response to renal ischemia. Observations of kidneys flushed with a renal preservation solution and stored at 0-41C also revealed progressive and significant loss of tubular integrity over time. Intravenous infusion of mannitol solution resulted in thinning of the tubular walls and an increase in the tubular lumen diameters. Mannitol infusion also prevented the cell swelling that otherwise resulted in shrinkage of proximal tubule lumens during ischemia. We conclude that OCT represents an exciting new approach to visualize, in real-time, pathological changes in the living kidney in a non-invasive fashion. Possible clinical applications are discussed.

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“…Limited histologic observation indicated glomerular and peritubular capillary injury in the ischemic kidney in some clinical cases of RAS 7 and in a swine graded renal ischemic model. 24 The current study describes alterations of microvascular architecture observed in RAS by using a powerful 3D imaging technique. Indeed, vascular rarefaction is known to occur in other ischemic organs, such as the hind limb 25 or heart.…”

Section: Discussionmentioning

confidence: 99%

Cortical Microvascular Remodeling in the Stenotic Kidney

Zhu

Chade

Rodriguez-Porcel

et al. 2004

ATVB

139

201

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Objective-Mechanisms of renal injury distal to renal artery stenosis (RAS) remain unclear. We tested the hypothesis that it involves microvascular remodeling consequent to increased oxidative stress. Methods and Results-Three groups of pigs (nϭ6 each) were studied after 12 weeks of RAS, RASϩantioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily), or controls. The spatial density and tortuousity of renal microvessels (Ͻ500 m) were tomographically determined by 3D microcomputed tomography. The in situ production of superoxide anion and the expression of vascular endothelial growth factor (VEGF), its receptor VEGFR-2, hypoxia-inducible-factor (HIF)-1␣, von Hippel-Lindau (VHL) protein, and NAD(P)H oxidase (p47phox and p67phox subunits) were determined in cortical tissue. RAS and RASϩantioxidant groups had similar degrees of stenosis and hypertension. The RAS group showed a decrease in spatial density of cortical microvessels, which was normalized in the RASϩantioxidant group, as was arteriolar tortuousity. RAS kidneys also showed tissue fibrosis (by trichrome and Sirius red staining), increased superoxide anion abundance, NAD(P)H oxidase, VHL protein, and HIF-1␣ mRNA expression. In contrast, expression of HIF-1␣, VEGF, and VEGFR-2 protein was downregulated. These were all significantly improved by antioxidant intervention. Conclusions-Increased oxidative stress in the stenotic kidney alters growth factor activity and plays an important role in renal microvascular remodeling, which can be prevented by chronic antioxidant intervention. (Arterioscler Thromb

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Morphological Changes and Alterations in Regional Intrarenal Blood Flow Induced by Graded Renal Ischemia

Cited by 44 publications

References 15 publications

Gq signaling causes glomerular injury by activating TRPC6

Gq signaling causes glomerular injury by activating TRPC6

High-resolution optical coherence tomography imaging of the living kidney

Cortical Microvascular Remodeling in the Stenotic Kidney

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