Response of descending vasa recta to luminal pressure

Zhang, Zhong; Pallone, Thomas L.

doi:10.1152/ajprenal.00394.2003

Cited by 30 publications

(23 citation statements)

References 46 publications

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“…Notably, the reaction of NO with hemoglobin is orders of magnitude faster than its consumption by O 2 Ϫ . Moreover, endothelial shearmediated increases in the basal rate of NO production could be a significant variable (58).…”

Section: Mechanisms Underlying H 2 O 2 -Induced Vasoconstrictionmentioning

confidence: 99%

“…Cao and colleagues (4) observed that blockade of NO generation led to substantial vasoconstriction that was partly reversed by scavenging O 2 Ϫ or inhibiting O 2 Ϫ generation. Those experiments were performed under conditions of luminal shear stimulation, i.e., during isolated vessel microperfusion, which markedly enhances endothelial NO generation (58). Other studies in explanted tissue preparations, in which DVR were not perfused, have elegantly shown that NO and O 2 Ϫ from adjacent epithelia can reach DVR pericytes to modify pericyte cytoplasmic Ca 2ϩ levels (10).…”

Section: Mechanisms Underlying H 2 O 2 -Induced Vasoconstrictionmentioning

confidence: 99%

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Cellular mechanisms underlying nitric oxide-induced vasodilation of descending vasa recta

Edwards

Cao

Pallone

2011

American Journal of Physiology-Renal Physiology

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signaling and MLC phosphorylation. At concentrations above 1 nM, O 2 Ϫ is predicted to modulate [Cacyt] and MCLP activity mostly by reducing NO bioavailability. The DVR vasoconstriction that is induced by high concentrations of H 2O2 can be explained by H2O2-mediated downregulation of MLCP and SERCA activity. We conclude that intrinsic generation of NO by the DVR wall may be sufficient to inhibit vasoconstriction by maintaining suppression of MLC phosphorylation. calcium signaling; hydrogen peroxide; superoxide; vascular smooth muscle NITRIC OXIDE (NO) acts as a local vasodilator in the renal medulla and plays an important role in the maintenance of medullary perfusion, medullary oxygenation, and blood pressure. Chronic inhibition of nitric oxide synthase (NOS) reduces medullary blood flow (MBF) and is associated with sodium retention and the development of hypertension (8, 41). Whereas NO increases MBF by promoting the vasodilation of descending vasa recta (DVR) or juxtamedullary arterioles, superoxide (O 2 Ϫ ) and hydrogen peroxide (H 2 O 2 ) act to reduce MBF by mechanisms that remain to be fully elucidated (17,37). In addition, NO inhibits, whereas O 2 Ϫ enhances, thick ascending limb sodium reabsorption (23). Hence, interactions between NO and O 2 Ϫ likely contribute to the long-term control of blood pressure; when the balance between these two radicals is shifted in favor of O 2 Ϫ (such as in diabetes and atherosclerosis, conditions that promote oxidative stress), renal vasoconstriction and tubular reabsorption increase, favoring hypertension (17).In a recent microperfusion study of DVR (4), we showed that intrinsic production of NO and reactive oxygen species (ROS) affects DVR vasoactivity. To elucidate the cellular pathways by which NO, O 2 Ϫ , and H 2 O 2 modulate DVR contraction, in the present study we expanded our mathematical model of Ca 2ϩ signaling in DVR pericytes to account for the effects of NO and ROS and to predict the degree of vessel contraction.Smooth muscle contraction is initiated by an increase in cytosolic Ca 2ϩ concentration ([Ca] cyt ). Increased binding of Ca 2ϩ to calmodulin (CaM) activates myosin light chain kinase (MLCK), which then phosphorylates myosin light chains (MLC) in the presence of ATP, thereby increasing the cycling rate of actin-myosin cross-bridge formation and generating the active force needed for muscle contraction. Most of the vasodilatory effects of NO on smooth muscle cells appear to be mediated by cGMP. Activity of the NO/cGMP pathway favors reduction in the fraction of phosphorylated myosin, via two different mechanisms: 1) an increase in the activity of myosin light chain phosphatase (MLCP), and 2) modulation of Ca 2ϩ transport that lowers [Ca] cyt , decreases Ca 2ϩ binding to CaM, and thereby reduces MLCK activity.We incorporated these and other signaling pathways in our mathematical model of DVR pericytes as described in MODEL DESCRIPTION. The data on which this and prior versions of the model are based have been largely derived from studies of DVR peric...

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Section: Mechanisms Underlying H 2 O 2 -Induced Vasoconstrictionmentioning

confidence: 99%

Section: Mechanisms Underlying H 2 O 2 -Induced Vasoconstrictionmentioning

confidence: 99%

Cellular mechanisms underlying nitric oxide-induced vasodilation of descending vasa recta

Edwards

Cao

Pallone

2011

American Journal of Physiology-Renal Physiology

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“…When L-NAME (10 Ϫ4 mol/L) was used, it was exchanged into the bath at the same time as the perfusate was exchanged. Perfusion was then restarted, providing flow as a stimulus to DVR endothelial production of NO (22). DAF-FM fluorescence images were captured at 30-second intervals throughout the 20-minute perfusion period.…”

Section: Protocolsmentioning

confidence: 99%

Iodixanol, Constriction of Medullary Descending Vasa Recta, and Risk for Contrast Medium–induced Nephropathy

Sendeski¹,

Patzak²,

Pallone³

et al. 2009

Radiology

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Purpose:To determine whether a type of contrast medium (CM), iodixanol, modifies outer medullary descending vasa recta (DVR) vasoreactivity and nitric oxide (NO) production in isolated microperfused DVR. Materials and Methods:Animal handling conformed to the Animal Care Committee Guidelines of all participating institutions. Single specimens of DVR were isolated from rats and perfused with a buffered solution containing iodixanol. A concentration of 23 mg of iodine per milliliter was chosen to mimic that expected to be used in usual examinations in humans. Luminal diameter was determined by using video microscopy, and NO was measured by using fluorescent techniques. Results:Iodixanol led to 52% reduction of DVR luminal diameter, a narrowing that might interfere with passage of erythrocytes in vivo. Vasoconstriction induced by angiotensin II was enhanced by iodixanol. Moreover, iodixanol decreased NO bioavailability by more than 82%. Use of 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (a superoxide dismutase mimetic) prevented both vasoconstriction with iodixanol alone and increased constriction with angiotensin II caused by CM. Conclusion:Iodixanol in doses typically used for coronary interventions constricts DVR, intensifies angiotensin II-induced constriction, and reduces bioavailability of NO. CM-induced nephropathy may be related to these events and scavenging of reactive oxygen species might exert a therapeutic benefit by preventing the adverse effects that a CM has on medullary perfusion. RSNA, 2009 Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, use the Radiology Reprints form at the end of this article. Contrast medium (CM)-induced nephropathy (CIN) is a lifethreatening complication of radiologic examinations and procedures in which an iodinated CM is used (1). In Europe and the United States, CIN accounts for more than 10% of all causes of hospital-acquired acute renal failure (2).Percutaneous coronary angiography is associated with a high risk of CIN in patients with preexisting chronic kidney disease: Roughly onehalf of these patients develop acute renal failure (3) that is associated with a 25% 1-year mortality rate (4). Several prior investigators have studied whether infusing sodium bicarbonate or scavenging reactive oxygen species (ROS) with ascorbic acid or N-acetylcysteine can prevent CIN (5-10). The intrarenal events that underlie CIN remain controversial, and the mechanism by which scavenging ROS might exert a therapeutic benefit remains to be determined.Evidence supports a high degree of vulnerability of the renal outer medulla to CM-induced damage (11). That propensity has been attributed to the nature of tubular-vascular relationships (12). Vulnerability of the thick ascending limbs to ischemic insult therefore may be an inescapable consequence of the anatomic arrangements in the outer medulla. In summary, descending vasa recta (DVR) are microvessels whose luminal diameters approach the d...

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“…NOS 1 29 and NOS 3 30 have been thought to be regulated primarily by increases in intracellular calcium and NOS 2 by changes in expression of the enzyme. 31 However, these views have recently been challenged by studies in a number of renal and other cell types.…”

Section: Regulation Of Nos Activitymentioning

confidence: 99%

“…It is unclear whether this is also true for renal vessels, because flowinduced activation of NOS 3 in the vasa recta does not appear to be caused by phosphorylation at serine 1179, but rather simply an increase in intracellular calcium. 30 In addition to serine 1179, at least 4 other phosphorylation sites on NOS 3 are known. 59 Insulin has also been suggested to enhance NOS 3 activity in the renal medulla by dephosphorylating threonine 495 in diabetic rats.…”

Section: Regulation Of Nos Activitymentioning

confidence: 99%

Recent Advances in the Regulation of Nitric Oxide in the Kidney

Herrera

Garvin

2005

Hypertension

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Abstract-Nitric oxide (NO) plays important roles in the regulation of renal function and the long-term control of blood pressure. New roles of NO have been proposed recently in diabetes, nephrotoxicity, and pregnancy. NO derived from all 3 NOS isoforms contributes to the overall regulation of kidney function, and recent advances in our understanding of their regulation have been made lately. In this regard, substrate and cofactor availability play important roles in regulating nitric oxide synthase (NOS) activity not only by limiting enzyme activity but also by influencing the coupling of NOS with its cofactors, tetrahydrobiopterin and NADPH. Protein-protein interactions are now recognized to be important negative and positive regulators of NOS. Phosphorylation is another component of the mechanism whereby NOS is activated or deactivated. Increased NOS expression can also influence enzyme activity; however, the degree of expression does not always correlate with enzyme activity because increased NO levels can result in inhibition of NOS. Finally, other potential regulators of NOS such as endogenous L-arginine analogs may also be important. In this article, we summarize recent advances in the regulation of activity and expression of the NOS isoforms within the kidney. renal function and long-term regulation of blood pressure. [1][2][3][4] This is best evidenced by the fact that inhibiting intrarenal NO production increased blood pressure. 5 In addition, reduced NO has been identified as a common denominator of many hypertensive models. 6 -9 The effects of NO on blood pressure via actions in the kidney occur through multiple mechanisms. These include increasing renal blood flow caused by vasodilatation, 10 increasing glomerular filtration, 11 inhibiting sodium transport along the nephron, 12-14 and regulating release of renin. 15 NO produced by each of the 3 nitric oxide synthases (NOS), NOS 1, NOS 2, and NOS 3, reportedly contributes to the regulation of renal function. Inhibition of NOS activity within the kidney is known to lead to sodium retention and hypertension. This review addresses recent advances in our understanding of the role played by renal NO in various physiological and pathophysiological conditions, as well as how NO production is regulated. Roles for Renal NOHistorically, NO produced by the kidney has been thought of primarily as a factor that regulates urinary volume and sodium excretion. The physiological effects of NO can be mediated via changes in renal hemodynamics and/or salt and water absorption by the nephron. NO reduces renal vascular tone in part by dilating the afferent arteriole. 16 It also increases glomerular filtration rate. 11 NO modulates renin secretion by the juxtaglomerular apparatus 15 and tubuloglomerular feedback. 3 Finally, NO regulates transport in various nephron segments as reviewed recently by Ortiz and Garvin. 12 More recently it has been recognized that in a number of pathophysiological conditions, the actions of NO on renal hemodynamics and/or nephron transport are ...

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Response of descending vasa recta to luminal pressure

Cited by 30 publications

References 46 publications

Cellular mechanisms underlying nitric oxide-induced vasodilation of descending vasa recta

Cellular mechanisms underlying nitric oxide-induced vasodilation of descending vasa recta

Iodixanol, Constriction of Medullary Descending Vasa Recta, and Risk for Contrast Medium–induced Nephropathy

Recent Advances in the Regulation of Nitric Oxide in the Kidney

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