Inhibition of proximal tubular fluid absorption by  nitric oxide and atrial natriuretic peptide in rat kidney

Eitle, Eveline; Hiranyachattada, Siriphun; Wang, Hui; Harris, Peter

doi:10.1152/ajpcell.1998.274.4.c1075

Cited by 82 publications

(69 citation statements)

References 30 publications

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“…We now believe the partial to substantial recovery of NO during elevated NaCl concentration at both 400 and 600 mOsm reflected the cells were simply expressing a decreased entry of sodium into the cells as part of feedback suppression of sodium entry into the cells. Studies by Levine et al [12], Ortiz et al [13], Roczniak and Burns [9], and Eitle et al [14] have shown NO suppresses transport of sodium ions in a negative feedback scenario and this area has been reviewed by Liang and Knox in 2000 [15]. From our observations, a similar process occurs in tissue slice specimens and is particularly apparent with low sodium stress conditions, such as 400 mOsm NaCl.…”

Section: Discussionsupporting

confidence: 77%

“…Using isolated thick ascending limb tubules of the rat, Ortiz et al [13] have shown NaCl increased NO production that suppressed the Na + /K + /2Cl + cotransport to limit further sodium uptake. In this same context, Eitle et al [14] using in vivo split droplet techniques in rat proximal tubules and Roczniak and Burns [9] using isolated rabbit proximal tubules found exogenous NO decreased NaCl coupled fluid transport and cell uptake of sodium. These various studies support the evolving hypothesis that entry of sodium ions into tubular cells initiated a set of mechanisms that used NO to suppress further sodium absorption.…”

Section: Introductionmentioning

confidence: 95%

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Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

et al. 2007

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Renal tubules process large amounts of NaCl that other investigators indicate increases tubular generation of nitric oxide. We questioned whether medullary or superficial cortical tubules would have the greater increase in nitric oxide concentration, [NO], when stressed by sodium and if the sodium/calcium exchanger was involved. Sodium stress in proximal tubules is due to the large amount of sodium absorbed and medullary tubules exist in a hypertonic sodium environment. To sodium stress the tissue, mouse kidney slices were exposed to monensin to allow passive entry of sodium ions from isotonic media and in separate studies, 400 and 600 mOsm NaCl was used. [NO] was measured with microelectrodes. Monensin (10 μM) caused a sustained increase in medullary and cortical [NO] to ∼180% of control and 400 mOsm NaCl caused a similar initial increase in [NO] that then subsided. 600 mOsm NaCl caused a more sustained increase in [NO] of >250% of control. L-NAME strongly attenuated the increased [NO] during sodium stress. The increase in [NO] during NaCl elevation was due to sodium ions because mannitol hyperosmolarity caused ∼20% of the increase in [NO]. Entry of sodium during NaCl hyperosmolarity was through bumetanide sensitive channels because the drug suppressed increased [NO]. Blockade of the sodium/calcium ion exchanger strongly suppressed the increased [NO] during monensin, to increase sodium entry into cells, and the elevated NaCl concentration. The data support a sodium -NO linkage that increased NO signaling in proportion to sodium stress by cortical tubules and was highly dependent upon sodium-calcium exchange.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 95%

Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

et al. 2007

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“…The rats were adapted to the cages by being restrained for 2 h on 2 consecutive days before the final collection day to obtain unstressed conditions. Briefly, 14 [C]tetraethylammonium bromide clearance was used as a marker for the effective renal plasma flow (ERPF), 3 [H]inulin clearance as a marker for the GFR, and lithium clearance (C Li) as a marker for the outflow of tubular fluid from the proximal tubules. Renal clearances (C) and fractional excretions (FE) were calculated by the standard formulas…”

Section: Seriesmentioning

confidence: 99%

“…However, besides the circulatory effects, NO also exerts direct effects on renal tubular function, including an inhibitory action on proximal tubular sodium handling. Excess NO has been shown to inhibit the Na-K-ATPase and the type 3 sodium/proton exchanger (NHE3) in proximal tubular cell lines (20,33,46), and micropuncture studies in rats have shown that NO significantly decreases proximal tubular fluid reabsorption (14,61). These micropuncture data from rats are supported by studies in humans showing that systemic administration of NOS inhibitors decreases fractional excretion of sodium (FE Na ) and fractional excretion of lithium (FE Li ; an index for the delivery of tubular fluid out of the proximal tubules) (4,6,36).…”

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confidence: 99%

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

Græbe¹,

Brønd²,

Christensen³

et al. 2004

American Journal of Physiology-Renal Physiology

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Graebe, Martin, Lone Brønd, Sten Christensen, Søren Nielsen, Niels V. Olsen, and Thomas E. N. Jonassen. Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats. Am J Physiol Renal Physiol 286: F288-F297, 2004. First published October 28, 2003 10.1152/ajprenal.00089.2003.-The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) starting on the day of common bile duct ligation (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with shamoperated rats and that L-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were performed, followed by Western blotting of the electroneutral type 3 sodium/ proton exchanger (NHE3) and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K-ATPase levels, indicating that tubular segments distal to the proximal tubules were responsible for the increased sodium reabsorption. L-NAME-treated CBL rats showed an increased proximal reabsorption measured by the lithium clearance method and showed a marked increase in NHE3 and Na-K-ATPase protein levels. Our results show that chronic L-NAME treatment exacerbates the sodium retention found in CBL rats by a significant increase in proximal tubular reabsorption. common bile duct ligation; type 3 sodium/proton exhanger; proximal tubular function; lithium clearance THE EARLY STATE OF COMPENSATED cirrhosis is associated with renal sodium and water retention combined with a hyperdynamic circulation, evident as systemic arterial vasodilation with decreased total peripheral resistance and increased cardiac output. In 1991, Vallance and Moncada (56) suggested that increased systemic nitric oxide (NO) formation induced by low-grade endotoxemia could be the mediator of the hyperdynamic circulation. Since then, several studies in both animals and humans have validated this hypothesis and increased NO synthesis is now believed to be one of the early pathophysiological mechanisms of cirrhosis, being essential for systemic arterial vasodilation (3,7,19,24,37,38).The peripheral arterial vasodilation theory stated by Schrier and co-workers (49) proposes that the vasodilation-mediated relative vascular underfilling in cirrhosis is the primary event responsible for the renal sodium and water retention via activation of baroreceptors and humoral antinatriuretic mechanisms. Normalization of the hyperdynamic circulation by blockade of NO synthase (NOS) would in this context be a straightforward approach to try to prevent the sodium retention in cirrhotic liver disease, and a few studies have shown that short-term NOS inhibition in cirrhotic rats actually ameliorates the impaired sodium e...

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“…NO-induced natriuresis and diuresis can occur in the absence of hemodynamic changes, indicating that NO directly inhibits Na and water absorption along the nephron. In vitro studies have shown that NO blunts transport in isolated proximal tubules (1), cortical collecting ducts (3,39,40), inner medullary collecting ducts (2), and thick ascending limbs (2,34,35). Additionally, NO has been reported to inhibit Na transport in several cultured renal cells (5,15,16).…”

mentioning

confidence: 99%

Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O₂⁻and is diminished by a high-salt diet

Varela

Herrera

Garvin

2004

American Journal of Physiology-Renal Physiology

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A high-salt diet enhances nitric oxide (NO)-induced inhibition of transport in the thick ascending limb (THAL). Long exposures to NO inhibit Na-K-ATPase in cultured cells. We hypothesized that NO inhibits THAL Na-K-ATPase after long exposures and a high-salt diet would augment this effect. Rats drank either tap water or 1% NaCl for 7-10 days. Na-K-ATPase activity was assessed by measuring ouabain-sensitive ATP hydrolysis by THAL suspensions. After 2 h, spermine NONOate (SPM; 5 M) reduced Na-K-ATPase activity from 0.44 Ϯ 0.03 to 0.30 Ϯ 0.04 nmol P i ⅐ g protein Ϫ1 ⅐ min Ϫ1 in THALs from rats on a normal diet (P Ͻ 0.03). Nitroglycerin also reduced Na-K-ATPase activity (P Ͻ 0.04). After 20 min, SPM had no effect (change Ϫ0.07 Ϯ 0.05 nmol Pi ⅐ g protein Ϫ1 ⅐ min Ϫ1 ). When rats were fed high salt, SPM did not inhibit Na-K-ATPase after 120 min. To investigate whether ONOO Ϫ formed by NO reacting with O 2 Ϫ was involved, we measured O 2 Ϫ production. THALs from rats on normal and high salt produced 35.8 Ϯ 0.3 andϪ production differed, we studied the effects of the O 2 Ϫ scavenger tempol. In the presence of 50 M tempol, SPM did not inhibit Na-K-ATPase after 120 min (0.50 Ϯ 0.05 vs. 0.52 Ϯ 0.07 nmol Pi ⅐ g protein Ϫ1 ⅐ min Ϫ1 ). Propyl gallate, another O 2 Ϫ scavenger, also prevented SPM-induced inhibition of Na-K-ATPase activity. SPM inhibited pump activity in tubules from rats on high salt when O 2 Ϫ levels were increased with xanthine oxidase and hypoxanthine. We concluded that NO inhibits Na-K-ATPase after long exposures when rats are on a normal diet and this inhibition depends on O 2 Ϫ . NO donors do not inhibit Na-K-ATPase in THALs from rats on high salt due to decreased O 2 Ϫ production.superoxide; nitric oxide; Na transport; hypertension NITRIC OXIDE (NO) is an important regulator of renal function, promoting natriuresis and diuresis (9). Intrarenal administration of NO synthesis inhibitors lowers urinary Na excretion (11-13, 17, 19, 20, 22, 38), whereas NO donors induce natriuresis (18,19). NO-induced natriuresis and diuresis can occur in the absence of hemodynamic changes, indicating that NO directly inhibits Na and water absorption along the nephron. In vitro studies have shown that NO blunts transport in isolated proximal tubules (1), cortical collecting ducts (3, 39, 40), inner medullary collecting ducts (2), and thick ascending limbs (2, 34, 35). Additionally, NO has been reported to inhibit Na transport in several cultured renal cells (5,15,16). We reported that the inhibition of net Na absorption caused by NO in the thick ascending limb and cortical collecting duct is due to reduced activity of the transporters responsible for Na entry into the cell, namely, Na/H exchange (4) and Na-K-2Cl cotransport (29) in the thick ascending limb and amiloridesensitive Na channels in the cortical collecting duct (40). We did not find inhibition of basolateral Na-K-ATPase after 20 min of exposure. However, others showed that NO inhibits Na-K-ATPase activity in cultured cells after longer exposures and that inhibition ...

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Inhibition of proximal tubular fluid absorption by nitric oxide and atrial natriuretic peptide in rat kidney

Cited by 82 publications

References 30 publications

Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O₂⁻and is diminished by a high-salt diet

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Inhibition of proximal tubular fluid absorption by nitric oxide and atrial natriuretic peptide in rat kidney

Cited by 82 publications

References 30 publications

Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O2−and is diminished by a high-salt diet

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Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O₂⁻and is diminished by a high-salt diet