Elevations in Renal Interstitial Hydrostatic Pressure and 20-Hydroxyeicosatetraenoic Acid Contribute to Pressure Natriuresis

Williams, Jan Michael; Sarkis, Albert; López, Bernardo; Ryan, Robert P.; Flasch, Averia K.; Roman, Richard J.

doi:10.1161/01.hyp.0000255753.89363.47

Cited by 66 publications

(64 citation statements)

References 49 publications

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“…These results are consistent with the concept that increases in AP inhibit sodium reabsorption by the main distal nephron sodium transporters, which are related to increased intrarenal NO levels in response to increases in AP. 6,34,40,41 …”

Section: Discussionmentioning

confidence: 99%

Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption

Zhao

Navar

2008

Hypertension

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Abstract-Acute angiotensin II (Ang II) infusions into mice increase arterial pressure (AP) and elicit pressure natriuresis.We used this model of pressure natriuresis to delineate the distal nephron responses to AP-mediated increases in distal sodium delivery. In the first group, we measured changes in urinary sodium excretion (U Na V) in male C57/BL6 anesthetized mice (nϭ9) before and during acute Ang II infusions (5 ng/g of body weight per minute). Acute Ang II infusions increased AP (98Ϯ3 to 126Ϯ5 mm Hg; PϽ0.001), urine flow (2.7Ϯ0.5 to 6.0Ϯ0.8 L/min; PϽ0.01), and U Na V (0.6Ϯ0.2 to 1.3Ϯ0.2 Eq/min; PϽ0.05). There were significant relationships between U Na V and urine flow (yϭ0.207xϩ0.030; PϽ0.0001) and between U Na V and AP (yϭ0.027xϪ2.100). In a separate series, distal sodium delivery and fractional reabsorption of distal sodium delivery were determined in control (nϭ12) and Ang II-infused mice (nϭ8) by comparing U Na V before and after blockade of the 2 major distal nephron sodium transporters with amiloride (5 mg/kg of body weight) plus bendroflumethiazide (12 mg/kg of body weight). A positive relationship was found between U Na V (yϭ0.015xϪ1.100; PϽ0.0001) or distal sodium delivery (yϭ0.027xϪ0.900; PϽ0.0001) and AP. An inverse relationship was found between fractional reabsorption of distal sodium delivery and AP (yϭϪ0.511xϩ128.300; PϽ0.01). These data indicate that Ang II-mediated pressure natriuresis involves an increase in distal sodium delivery combined with a reduced distal nephron fractional sodium reabsorption, suggesting that increased AP prevents the distal nephron transport mechanisms from accommodating the increased distal delivery. Key Words: Ang II Ⅲ arterial pressure Ⅲ renal sodium reabsorption Ⅲ distal nephron segments Ⅲ amiloride Ⅲ bendroflumethiazide Ⅲ fractional distal sodium reabsorption I t is well known that increases in arterial pressure (AP) lead to the increases in renal sodium excretion, a phenomenon commonly referred to as pressure natriuresis. [1][2][3][4][5][6][7][8] The changes in renal sodium excretion in response to changes in AP provide a link between the mechanisms regulating sodium excretion and those regulating AP. 1 Because glomerular filtration rate (GFR) and filtered sodium load are autoregulated over the same AP range, the mechanism of pressure natriuresis involves decreased tubular sodium reabsorption in response to increased AP; 6 however, the relative contributions of the various nephron segments responsible have not been fully defined. 5,9 -12 Acute angiotensin II (Ang II) infusions in mice and rats increase AP and elicit pressure natriuresis, suggesting that Ang II infusion is a useful model to delineate the relative contributions of the various nephron segments to increases in AP.The development of a mouse model with minimal surgical interventions to study pressure natriuresis would allow evaluation of the roles of specific tubular transport systems by using various gene targeted models. Although several studies have focused on the AP effects on proximal nephro...

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Section: Discussionmentioning

confidence: 99%

Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption

Zhao

Navar

2008

Hypertension

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“…This increase in interstitial pressure in turn signals mechanisms which inhibit Na ϩ reabsorption by the proximal tubules. This response is at least partially mediated by an increase in 20-hydroxyeicosatetraenoic acid (20-HETE), which in turn inhibits Na ϩ -K ϩ -ATPase activity and an internalization of apical Na ϩ /H ϩ exchangers, resulting in a greater delivery of NaCl to the mTAL and distal tubules (196,202). Reductions in Na ϩ reabsorption in deeper nephron segments also occur, which are likely to be a result of washout of the medullary solute gradient and reduced passive reabsorption of sodium (30).…”

Section: ·ϫmentioning

confidence: 99%

“…With the outer medulla operating on the brink of hypoxia (18,50), either a reduction of blood supply or an increased metabolic load can generate greater amounts of ROS production in the mTAL. The metabolic work of the mTAL is increased as more Na ϩ is delivered to the loop of Henle, an event that occurs with a rise in renal perfusion pressure or a greater filtration of NaCl as seen with high-salt feeding, hypertension, and the early stages of diabetes (134,154,196,202). It is also relevant that increased delivery of NaCl to the loop of Henle driven by increased filtration is also the basis of the well-characterized tubuloglomerular feedback (TGF) responses initiated from the macula densa cells situated at the mTAL transition into the distal tubules (73).…”

Section: ·ϫmentioning

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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“…The major products in most tissues are the -hydroxylated metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) and regio-and stereo-specific epoxyeicosatrienoic acids. 20-HETE, a -hydroxylation product of arachidonic acid catalyzed by CYP4A, is a paracrine and autocrine mediator of numerous cellular processes (20,29,35). It is produced in vascular smooth muscle, renal, cerebral, pulmonary, mesenteric, and skeletal muscle beds and acts on the microvasculature and kidney tubules (11,18,22,33,38).…”

mentioning

confidence: 99%

20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells

Dhanasekaran

Bodiga

Gruenloh

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Hydroxyeicosatetraenoic acid (20-HETE) is an endogenous cytochrome P-450 product present in vascular smooth muscle and uniquely located in the vascular endothelium of pulmonary arteries (PAs). 20-HETE enhances reactive oxygen species (ROS) production of bovine PA endothelial cells (BPAECs) in an NADPH oxidase-dependent manner and is postulated to promote angiogenesis via activation of this pathway in systemic vascular beds. We tested the capacity of 20-HETE or a stable analog of this compound, 20-hydroxy-eicosa-5(Z),14(Z)-dienoic acid, to enhance survival and protect against apoptosis in BPAECs stressed with serum starvation. 20-HETE produced a concentration-dependent increase in numbers of starved BPAECs and increased 5-bromo-2Ј-deoxyuridine incorporation. Caspase-3 activity, nuclear fragmentation studies, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays supported protection from apoptosis and enhanced survival of starved BPAECs treated with a single application of 20-HETE. Protection from apoptosis depended on intact NADPH oxidase, phosphatidylinositol 3 (PI3)-kinase, and ROS production. 20-HETE-stimulated ROS generation by BPAECs was blocked by inhibition of PI3-kinase or Akt activity. These data suggest 20-HETEassociated protection from apoptosis in BPAECs required activation of PI3-kinase and Akt and generation of ROS. 20-HETE also protected against apoptosis in BPAECs stressed by lipopolysaccharide, and in mouse PAs exposed to hypoxia reoxygenation ex vivo. In summary, 20-HETE may afford a survival advantage to BPAECs through activation of prosurvival PI3-kinase and Akt pathways, NADPH oxidase activation, and NADPH oxidase-derived superoxide.reduced nicotinamide adenine dinucleotide phosphatase oxidase; reactive oxygen species; phosphatidylinositol 3-kinase; Akt; hypoxia CYTOCHROME P-450 (CYP) ENZYMES can metabolize arachidonic acid into numerous eicosanoids, with the relative abundance dependent on the tissue and species (21). The major products in most tissues are the -hydroxylated metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) and regio-and stereo-specific epoxyeicosatrienoic acids. 20-HETE, a -hydroxylation product of arachidonic acid catalyzed by CYP4A, is a paracrine and autocrine mediator of numerous cellular processes (20,29,35). It is produced in vascular smooth muscle, renal, cerebral, pulmonary, mesenteric, and skeletal muscle beds and acts on the microvasculature and kidney tubules (11,18,22,33,38).Our laboratory has recently reported that 20-HETE/CYP4 enhances reactive oxygen species (ROS) production in bovine pulmonary artery (PA) endothelial cells (BPAECs) in a manner that is associated with activation of NADPH oxidase (24). 20-HETE has been linked to ROS production in other vascular beds (19), with 20-HETE-stimulated production of ROS being reported to exert either positive or negative effects in a tissueand concentration-specific manner (e.g., Refs. 9, 17). In addition, NADPH oxidase is proposed to have a key role in growth and migration of human coronary endot...

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Elevations in Renal Interstitial Hydrostatic Pressure and 20-Hydroxyeicosatetraenoic Acid Contribute to Pressure Natriuresis

Cited by 66 publications

References 49 publications

Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption

Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption

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

20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells

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