Evidence for the presence of smooth muscle α-actin  within pericytes of the renal medulla

Park, Frank; Mattson, David L.; Roberts, L. A.; Cowley, Allen W.

doi:10.1152/ajpregu.1997.273.5.r1742

Cited by 62 publications

(68 citation statements)

References 13 publications

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“…Consistent with our results, a recent report has showed HSP60 upregulation in total protein extracts from diabetic rat kidneys (3,31). The distribution of HSP72 staining was suggestive of localization to both collecting ducts and thick ascending limbs, while HSP25 was overexpressed by the interstitial vessels, possibly in the pericytes surrounding the descending vasa recta, which are known to have a highly structured actin cytoskeleton (22). Although STZ is known to induce tubular damage, this occurs predominantly in cells of the S1 portion of the proximal tubuli, which are located in the renal cortex (29,37).…”

Section: Discussionsupporting

confidence: 92%

Heat shock protein expression in diabetic nephropathy

Barutta¹,

Pinach²,

Giunti³

et al. 2008

American Journal of Physiology-Renal Physiology

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Heat shock protein (HSP) HSP27, HSP60, HSP70, and HSP90 are induced by cellular stresses and play a key role in cytoprotection. Both hyperglycemia and glomerular hypertension are crucial determinants in the pathogenesis of diabetic nephropathy and impose cellular stresses on renal target cells. We studied both the expression and the phosphorylation state of HSP27, HSP60, HSP70, and HSP90 in vivo in rats made diabetic with streptozotocin and in vitro in mesangial cells and podocytes exposed to either high glucose or mechanical stretch. Diabetic and control animals were studied 4, 12, and 24 wk after the onset of diabetes. Immunohistochemical analysis revealed an overexpression of HSP25, HSP60, and HSP72 in the diabetic outer medulla, whereas no differences were seen in the glomeruli. Similarly, exposure neither to high glucose nor to stretch altered HSP expression in mesangial cells and podocytes. By contrast, the phosphorylated form of HSP27 was enhanced in the glomerular podocytes of diabetic animals, and in vitro exposure of podocytes to stretch induced HSP27 phosphorylation via a P38-dependent mechanism. In conclusion, diabetes and diabetesrelated insults differentially modulate HSP27, HSP60, and HSP70 expression/phosphorylation in the glomeruli and in the medulla, and this may affect the ability of renal cells to mount an effective cytoprotective response. mesangial cells; glomerular epithelial cells; mechanical stretch DIABETIC NEPHROPATHY (DN), the leading cause of end-stage renal failure in the Western world, is characterized by increased albumin excretion rate (AER) and progressive decline in renal function (9,20). Both hyperglycemia and glomerular capillary hypertension are considered major determinants in the onset and the progression of the complication (5), and in vitro studies on renal cells exposed to high glucose and/or mechanical stretch have partially clarified the underlying cellular mechanisms for this disorder (13).Heat shock proteins (HSP) are ubiquitous, highly evolutionary conserved intracellular proteins categorized according to their molecular weight (10). Thermal, oxidative, hemodynamic, osmotic, and hypoxic stresses (17) induce HSP60, HSP27 (human)/HSP25 (rodents), and HSP70 (human)/HSP72 (rodents), and HSP90 expression, and this stress response results in cytoprotection (18). Specifically, HSP prevent nonspecific protein assembly, assist in denatured protein refolding, and interfere with proapoptotic pathways. Both hyperglycemia and glomerular capillary hypertension impose cellular stresses on renal target cells and they are thus potential inducers of a stress response that may counterbalance the deleterious effects of these insults. In addition, enhanced expression/phosphorylation of HSP27, an actin-specific molecular chaperone, has been reported in podocytes in experimental nephrotic syndrome (32), suggesting a role for HSP27 in the pathophysiological changes of the podocyte cytoskeleton during the development of proteinuria. Liu et al. (19) have demonstrated that HSP47, a procolla...

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Section: Discussionsupporting

confidence: 92%

Heat shock protein expression in diabetic nephropathy

Barutta¹,

Pinach²,

Giunti³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…The diameter of the entire vasa recta bundle does not exceed the estimated diffusion distance of NO within biological fluids (0.2-0.25 mm) as indicated above (46,47). Finally, although the deep vasa recta of the inner medulla remain to be studied, it is likely that these vessels may be controlled in a similar fashion by the high levels of NO produced by the epithelial cells of the IMCD, because pericytes have been shown to exist surrounding these vasa recta, although less densely distributed (88).…”

Section: Evidence For Paracrine and Autocrine No Function In The Renamentioning

confidence: 77%

“…2C. The DVR pericytes contain ␣-smooth muscle actin (88), and the ability of the pericytes to constrict and reduce the diameter of DVR has been demonstrated by Pallone and colleagues (86) using isolated perfused vasa recta vessels from the outer medulla. For example, these vessels have been shown to respond to vasoconstrictors such as ANG II, as shown in Fig.…”

Section: Evidence For Paracrine and Autocrine No Function In The Renamentioning

confidence: 94%

Role of renal NO production in the regulation of medullary blood flow

Cowley

Mori

Mattson

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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176

202

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. Role of renal NO production in the regulation of medullary blood flow. Am J Physiol Regul Integr Comp Physiol 284: R1355-R1369, 2003 10.1152/ajpregu.00701.2002The unique role of nitric oxide (NO) in the regulation of renal medullary function is supported by the evidence summarized in this review. The impact of reduced production of NO within the renal medulla on the delivery of blood to the medulla and on the long-term regulation of sodium excretion and blood pressure is described. It is evident that medullary NO production serves as an important counterregulatory factor to buffer vasoconstrictor hormoneinduced reduction of medullary blood flow and tissue oxygen levels. When NO synthase (NOS) activity is reduced within the renal medulla, either pharmacologically or genetically [Dahl salt-sensitive (S) rats], a super sensitivity to vasoconstrictors develops with ensuing hypertension. Reduced NO production may also result from reduced cellular uptake of L-arginine in the medullary tissue, resulting in hypertension. It is concluded that NO production in the renal medulla plays a very important role in sodium and water homeostasis and the long-term control of arterial pressure. renal medulla; Dahl salt-sensitive rats; hypertension; L-arginine THE RENAL MEDULLARY CIRCULATION is now recognized to be of importance for reasons that extend far beyond providing the economy of countercurrent exchange to concentrate large volumes of filtrate to produce small volumes of concentrated urine. It is now recognized that medullary blood flow (MBF) can play an important role in determining long-term levels of arterial pressure and that 15-30% reductions of blood flow to the renal medulla in the face of imperceptibly small changes of total renal blood flow can lead to the development of hypertension (16,21). Evidence is reviewed showing that nitric oxide (NO) plays a unique role in the acute and chronic regulation of renal MBF, sodium homeostasis, and arterial pressure. More specifically, the role of NO in the regulation of MBF, in linking tubular metabolic needs with delivery of nutrients and as a counterregulatory system to protect the medulla from the consequences of underperfusion, are the focus of this review. The influence of NO on the renal cortex and such issues that relate to pressure-natriuresis, autoregulation of total renal blood flow, tubuloglomerular feedback, and glomerular filtration rate (GFR) regulation are important subjects of renal function that either have been reviewed by others (2,29,43,55,96) or are beyond the scope of this relatively brief review.

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“…The DVR wall is characterized by smooth muscle remnants that surround a continuous endothelium and impart contractile function. The pericytes persist into the inner medulla but eventually disappear (111,120). Near their termination, DVR become fenestrated and give rise to a sparse capillary plexus.…”

Section: Renal Medullary Microvascular Anatomymentioning

confidence: 99%

Physiology of the renal medullary microcirculation

Pallone

Zhang

Rhinehart

2003

American Journal of Physiology-Renal Physiology

187

193

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Pallone, Thomas L., Zhong Zhang, and Kristie Rhinehart. Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol 284: F253-F266, 2003; 10.1152/ajprenal.00304.2002.-Perfusion of the renal medulla plays an important role in salt and water balance. Pericytes are smooth muscle-like cells that impart contractile function to descending vasa recta (DVR), the arteriolar segments that supply the medulla with blood flow. DVR contraction by ANG II is mediated by depolarization resulting from an increase in plasma membrane Cl Ϫ conductance that secondarily gates voltage-activated Ca 2ϩ entry. In this respect, DVR may differ from other parts of the efferent microcirculation of the kidney. Elevation of extracellular K ϩ constricts DVR to a lesser degree than ANG II or endothelin-1, implying that other events, in addition to membrane depolarization, are needed to maximize vasoconstriction. DVR endothelial cytoplasmic Ca 2ϩ is increased by bradykinin, a response that is inhibited by ANG II. ANG II inhibition of endothelial Ca 2ϩ signaling might serve to regulate the site of origin of vasodilatory paracrine agents generated in the vicinity of outer medullary vascular bundles. In the hydropenic kidney, DVR plasma equilibrates with the interstitium both by diffusion and through water efflux across aquaporin-1. That process is predicted to optimize urinary concentration by lowering blood flow to the inner medulla. To optimize urea trapping, DVR endothelia express the UT-B facilitated urea transporter. These and other features show that vasa recta have physiological mechanisms specific to their role in the renal medulla. vasa recta; perfusion; hypertension; oxygenation; urinary concentration; patch clamp; calcium; fura 2 THE MICROCIRCULATION OF THE kidney is regionally specialized. In the cortex, afferent and efferent arterioles govern the driving forces that promote glomerular filtration. A dense peritubular capillary plexus arising from efferent arterioles surrounds the proximal and distal convoluted tubules to accommodate enormous reabsorption of glomerular filtrate. In contrast, vasa recta serve needs specific to the medulla. Through the counterflow arrangement of descending (DVR) and ascending vasa recta (AVR), countercurrent exchange traps NaCl and urea deposited to the interstitium by collecting ducts and the loops of Henle. This is vital to maintain corticomedullary osmotic gradients but conflicts with the need to supply nutrient blood flow to medullary tissue. Metabolic substrates that enter the medulla in DVR blood diffuse to the AVR to be shunted back to the cortex. To deal with the threat of medullary hypoxia resulting from this process, the kidney has evolved a capacity to exert subtle control over regional perfusion of the outer and inner medulla. The details are far from clear, but much experimental evidence points to the complex interactions of many autocoids and paracrine agents to modulate vasomotor tone at various sites along the microvascular circuit. The goal of this review is to summarize ...

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Evidence for the presence of smooth muscle α-actin within pericytes of the renal medulla

Cited by 62 publications

References 13 publications

Heat shock protein expression in diabetic nephropathy

Heat shock protein expression in diabetic nephropathy

Role of renal NO production in the regulation of medullary blood flow

Physiology of the renal medullary microcirculation

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