Renal pericytes: regulators of medullary blood flow

Kennedy-Lydon, Teresa M; Crawford, Cynda; Wildman, Scott S.P.; Peppiatt‐Wildman, Claire M.

doi:10.1111/apha.12026

Cited by 72 publications

(58 citation statements)

References 131 publications

(312 reference statements)

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“…Vascular resistance in kidneys of L‐NAME–treated rats was greater in the medulla than in the cortex, which was caused by a shift of intrarenal blood flow and hence oxygen delivery from medulla to cortex 49. Arterioles of juxtamedullary glomeruli, which provide blood flow to the medulla, contain more smooth muscle than those of glomeruli in the cortex 50, 51. Consequently, blood supply to the medulla is more dependent on the NO vasodilatory reserve than the cortex 52.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Emans

Janssen

Joles

et al. 2018

JAHA

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BackgroundRenal hypoxia, implicated as crucial factor in onset and progression of chronic kidney disease, may be attributed to reduced nitric oxide because nitric oxide dilates vasculature and inhibits mitochondrial oxygen consumption. We hypothesized that chronic nitric oxide synthase inhibition would induce renal hypoxia.Methods and ResultsOxygen‐sensitive electrodes, attached to telemeters, were implanted in either renal cortex (n=6) or medulla (n=7) in rats. After recovery and stabilization, baseline oxygenation (pO 2) was recorded for 1 week. To inhibit nitric oxide synthase, N‐ω‐nitro‐l‐arginine (L‐NNA; 40 mg/kg/day) was administered via drinking water for 2 weeks. A separate group (n=8), instrumented with blood pressure telemeters, followed the same protocol. L‐NNA rapidly induced hypertension (165±6 versus 108±3 mm Hg; P<0.001) and proteinuria (79±12 versus 17±2 mg/day; P<0.001). Cortical pO 2, after initially dipping, returned to baseline and then increased. Medullary pO 2 decreased progressively (up to −19±6% versus baseline; P<0.05). After 14 days of L‐NNA, amplitude of diurnal medullary pO 2 was decreased (3.7 [2.2–5.3] versus 7.9 [7.5–8.4]; P<0.01), whereas amplitudes of blood pressure and cortical pO 2 were unaltered. Terminal glomerular filtration rate (1374±74 versus 2098±122 μL/min), renal blood flow (5014±336 versus 9966±905 μL/min), and sodium reabsorption efficiency (13.0±0.8 versus 22.8±1.7 μmol/μmol) decreased (all P<0.001).ConclusionsFor the first time, we show temporal development of renal cortical and medullary oxygenation during chronic nitric oxide synthase inhibition in unrestrained conscious rats. Whereas cortical pO 2 shows transient changes, medullary pO 2 decreased progressively. Chronic L‐NNA leads to decreased renal perfusion and sodium reabsorption efficiency, resulting in progressive medullary hypoxia, suggesting that juxtamedullary nephrons are potentially vulnerable to prolonged nitric oxide depletion.

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Section: Discussionmentioning

confidence: 99%

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Emans

Janssen

Joles

et al. 2018

JAHA

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“…Cross talk of free radicals between cells and neighboring tissues has been the subject of much interest and controversy. Although it remains unclear how sufficient amounts of O 2 ·Ϫ , H 2 O 2 , or NO could be released from mTAL epithelial cells and escape enzymatic degradation or interactions with other oxidizing molecules, there is compelling experimental evidence that this can occur under certain conditions (32,90,132,140). Using freshly isolated thin tissue strips from the inner stripe of the outer medulla and time-resolved fluorescence videomicroscopy techniques, it was found that mTAL of SS rats exhibited greater rates of O 2 ·Ϫ production in response to ANG II stimulation compared with SS.…”

Section: Excess O 2 ·ϫ and H 2 O 2 Production Relative To No In Mtal mentioning

confidence: 99%

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Cowley

Abe

Mori

et al. 2015

American Journal of Physiology-Renal Physiology

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logical evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na ϩ reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension.superoxide (O 2 ·Ϫ ); hydrogen peroxide (H2O2); nitric oxide (NO); NAD(P)H oxidase; mTAL; medullary blood flow; kidney; Dahl SS rats REACTIVE OXYGEN SPECIES (ROS) are chemically reactive molecules derived from oxygen, whose role as mediators of intracellular signaling cascades is well recognized. The following is a brief review of physiological data linking superoxide (O 2 ·Ϫ ), hydrogen peroxide (H 2 O 2 ), and nitric oxide (NO) production in the medullary thick ascending limbs of Henle (mTAL) to sodium (Na ϩ ) homeostasis, the regulation of medullary blood flow (MBF), and the long-term regulation of arterial blood pressure. MBF to the renal medulla can be importantly controlled by the constriction and dilation of the descending vasa recta (VR) capillaries, which branch from the efferent arterioles of the juxtamedullary glomeruli (49, 147, 149) and whose tone is controlled by the smooth muscle-like pericytes (49, 90, 146 -149). The role of NO cross talk from mTAL to surrounding VR in the renal medulla has been reviewed in detail elsewhere (19, 33) and will be discussed here largely with regard to its ROS-related counterregulatory functions. The present review will first summarize data showing that either the excess endogenous production or reduced scavenging of O 2 ·Ϫ or H 2 O 2 within the renal medulla results in a decrease in MBF and Na ϩ excretion, leading to hypertension and renal injury. Second, evidence will be summarized supporting the hypothesis that a high dietary salt intake results in increased luminal flow and delivery of NaCl to the mTAL, thereby signaling via both mechanical forces (stretch and shear) and increased Na ϩ transport, an increased mitochondrial and membrane NA-D(P)H oxidase production of O 2 ·Ϫ and H 2 O 2 . Third, studies will be reviewed showing that reduction of MBF leads to hypertension a...

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“…Kidney pericytes regulate renal blood flow 6 and are emerging key players in the development of renal fibrosis and chronic kidney disease (CKD). Pericytes contribute to the renal myofibroblast pool in renal fibrogenesis via pericyte–myofibroblast trans-differentiation, and their detachment of capillaries might trigger capillary rarefaction, one of the hallmarks of acute kidney injury to CKD progression.…”

mentioning

confidence: 99%

Kidney Pericytes: Roles in Regeneration and Fibrosis

Kramann

Humphreys

2014

Seminars in Nephrology

127

108

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Summary Renal pericytes have been neglected for many years, but recently they have become an intensively studied cell population in renal biology and pathophysiology. Pericytes are stromal cells that support vasculature, and a subset of pericytes are mesenchymal stem cells. In kidney, pericytes have been reported to play critical roles in angiogenesis, regulation of renal medullary and cortical blood flow, and serve as progenitors of interstitial myofibroblasts in renal fibrogenesis. They interact with endothelial cells through distinct signaling pathways and their activation and detachment from capillaries after acute or chronic kidney injury may be critical for driving chronic kidney disease progression. By contrast, during kidney homeostasis it is likely that pericytes serve as a local stem cell population that replenishes differentiated interstitial and vascular cells lost during aging. This review describes both the regenerative properties of pericytes as well as involvement in pathophysiologic conditions such as fibrogenesis.

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Renal pericytes: regulators of medullary blood flow

Cited by 72 publications

References 131 publications

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Kidney Pericytes: Roles in Regeneration and Fibrosis

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