Regulation of Renal Na-K-Cl Cotransporter NKCC2 by Humoral Natriuretic Factors: Relevance in Hypertension

Garay, Ricardo P.; Álvarez-Guerra, Miriam; Alda, J. O.; Nazaret, Corinne; Soler, A; Vargas, Félix

doi:10.3109/10641969809053245

Cited by 10 publications

(4 citation statements)

References 26 publications

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“…In an in vivo perfusion system of rabbit lacrimal glands, it also has been shown that systemic furosemide significantly reduces carbachol-induced fluid delivery to the ocular surface (5), findings that suggest a similar role for the NKCC1 transporter in other species. In other cell types, stimulation results in activation of NKCC1 and/or upregulation of its expression (11,13,25). In some tissues, the decrease in intracellular Cl Ϫ ions that occurs upon cell activation stimulates NKCC1 (40).…”

Section: Discussionmentioning

confidence: 98%

Fluid secretion and the Na⁺-K⁺-2Cl⁻ cotransporter in mouse exorbital lacrimal gland

Walcott

Moore²,

Brink³

2005

American Journal of Physiology-Cell Physiology

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We have previously suggested that fluid flow in the mouse exorbital lacrimal gland is driven by the opening of apical Cl- and K+ channels. These ions move into the lumen of the gland and water follows by osmosis. In many tissues, the Na+-K+-2Cl- cotransporter (NKCC1) replaces the Cl- and K+ ions that move into the lumen. We hypothesize that mouse exorbital lacrimal glands would have NKCC1 co-transporters and that they would be important in fluid transport by this gland. We used immunocytochemistry to localize NKCC1-like immunoreactivity to the membranes of the acinar cells as well as to the basolateral membranes of the duct cells. We developed a method to measure tear flow and its composition from mouse glands in situ. Stimulation with the acetylcholine agonist carbachol produced a peak flow followed by a plateau. Ion concentration measurements of this stimulated fluid showed it was high in K+ and Cl-. Treatment of the gland with furosemide, a blocker of the NKCC1 cotransporter, reduced the plateau phase of fluid flow by approximately 30%. Isolated cells exposed to a hypertonic shock shrank by approximately 20% and then showed a regulatory volume increase (RVI). Both the RVI and swelling were blocked by treatment with furosemide. Cells isolated from these glands shrink by approximately 10% in the presence of carbachol. Blocking NKCC1 with furosemide reduced the amount of shrinkage by approximately 50%. These data suggest that NKCC1 plays an important role in fluid secretion by the exorbital gland of mice.

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Section: Discussionmentioning

confidence: 98%

Fluid secretion and the Na⁺-K⁺-2Cl⁻ cotransporter in mouse exorbital lacrimal gland

Walcott

Moore²,

Brink³

2005

American Journal of Physiology-Cell Physiology

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“…Recently, circulating and urinary compounds other than OLF, including marinobufagenin-like factor, 20 and substances structurally unrelated to steroids, such as those proposed by Kramer and coworkers 21 and Garay et al, 22 were shown to be increased under conditions of volume expansion. The effects of these compounds on renal function are not clear.…”

Section: Discussionmentioning

confidence: 99%

Plasma Ouabain-Like Factor During Acute and Chronic Changes in Sodium Balance in Essential Hypertension

Manunta¹,

Messaggio²,

Ballabeni³

et al. 2001

Hypertension

102

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Abstract-An ouabain-like factor has been implicated repeatedly in salt-sensitive hypertension as a natriuretic agent.However, the response of plasma ouabain-like factor to acute and chronic variation of body sodium is unclear. We studied 138 patients with essential hypertension who underwent an acute volume expansion/contraction maneuver (2 days) and 20 patients who entered a blind randomized crossover design involving chronically controlled sodium intake and depletion (170 to 70 mmol/d; 2 weeks each period). In both studies, plasma levels of ouabain-like factor were higher during sodium depletion (acute: 338.8Ϯ17.4 and 402.7Ϯ22.8 pmol/L for baseline and low sodium, respectively, PϽ0.01; chronic: 320.4Ϯ32.0 versus 481.0Ϯ48.1 pmol/L, Pϭ0.01). No significant change in plasma ouabain-like factor was observed after a 2-hour saline infusion (333.4Ϯ23.9 pmol/L) or controlled sodium (402.1Ϯ34.9 pmol/L). When patients were divided into salt-sensitive or salt-resistant groups, no differences in plasma ouabain-like factor were observed in the 2 groups at baseline or in response to the 2 protocols: salt resistant (nϭ69, 340.1Ϯ25.9 pmol/L) versus salt sensitive (nϭ69, 337.4Ϯ23.6 pmol/L) and chronic salt resistant (nϭ11, 336.0Ϯ53.2) versus salt sensitive (nϭ9, 301.1Ϯ331.4 pmol/L). However, circulating ouabain-like factor was increased by sodium depletion in both groups. These results demonstrate that circulating ouabain-like factor is raised specifically by maneuvers that promote the loss of body sodium. Acute expansion of body fluids with isotonic saline is not a stimulus to plasma ouabain-like factor. Moreover, basal levels of plasma ouabain-like factor do not differ among patients with salt-sensitive or salt-resistant hypertension. Taken together, these new results suggest that ouabain-like factor is involved in the adaptation of humans to sodium depletion and argue against the hypothesis that ouabain-like factor is a natriuretic hormone. Key Words: sodium pump inhibitor Ⅲ endogenous Ⅲ salt sensitivity Ⅲ high blood pressure T he involvement of a natriuretic hormone in the control of sodium homeostasis was hypothesized Ϸ40 years ago.

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“…The role of enhanced Na-K-2Cl cotransport in Dahl rats has already been suggested by old studies of erythrocyte ion transport (Knorr et al 1985, Zicha andDuhm 1990). Later Garay and coworkers focused their attention on both NKCC1 (erythrocytes) and NKCC2 (kidney) in Dahl rats, demonstrating a circulating inhibitor of Na-K-2Cl cotransporter in plasma of salt hypertensive Dahl rats (Alvarez-Guerra and Garay 1997, Garay et al 1998, Alvarez-Guerra et al 2002. In fact, our SS/Jr rats fed a low-salt diet were insensitive to HCTZ (Fig.…”

Section: Discussionmentioning

confidence: 93%

Is Renal β-Adrenergic-WNK4-NCC Pathway Important in Salt Hypertension of Dahl Rats?

Zicha

Hojná²,

Vaňourková³

et al. 2019

Physiol Res

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In 2011 Fujita and coworkers proposed that β-adrenergic stimulation causes decreased serine/threonine-protein kinase WNK4 transcription leading to the activation of Na-Cl cotransporter (NCC) which participates in salt sensitivity and salt hypertension development in rodents. The aim of our study was to investigate whether the above hypothesis is also valid for salt hypertension of Dahl rats, which are characterized by high sympathetic tone and abnormal renal sodium handling. Male 8-week-old salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats were fed either low-salt diet (LS, 0.4 % NaCl) or high-salt diet (HS, 4 % NaCl) for 6 weeks. Half of the animals on either diet were chronically treated with non-selective β-blocker propranolol (100 mg/kg/day). At the end of the experiment diuresis and sodium excretion were measured prior and after hydrochlorothiazide injection (HCTZ, 10 mg/kg i.p.). Furthermore, blood pressure (BP), heart rate (HR), sympathetic (pentolinium 5 mg/kg i.v.) and NO-dependent (L-NAME 30 mg/kg i.v.) BP components were determined. Chronic HS diet feeding increased BP through sympathoexcitation in SS/Jr but not in SR/Jr rats. Concomitant propranolol treatment did not lower BP in either experimental group. Under the conditions of low salt intake HCTZ increased diuresis, natriuresis and fractional sodium excretion in SR/Jr but not in SS/Jr rats. HS diet feeding attenuated renal response to HCT in SR/Jr rats, whereas no HCTZ effect was observed in SS/Jr rats fed HS diet. Propranolol treatment did not modify diuresis or natriuresis in any experimental group. In conclusions, our present data do not support the idea on the essential importance of renal β-adrenergic-WNK4-NCC pathway in pathogenesis and/or maintenance of salt hypertension in Dahl rats. Key words Sympathetic nervous system • β-adrenergic blockade • Renal sodium excretion • NCC cotransporter • Hydrochlorothiazide • Serine/threonine-protein kinase WNK4

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Regulation of Renal Na-K-Cl Cotransporter NKCC2 by Humoral Natriuretic Factors: Relevance in Hypertension

Cited by 10 publications

References 26 publications

Fluid secretion and the Na⁺-K⁺-2Cl⁻ cotransporter in mouse exorbital lacrimal gland

Fluid secretion and the Na⁺-K⁺-2Cl⁻ cotransporter in mouse exorbital lacrimal gland

Plasma Ouabain-Like Factor During Acute and Chronic Changes in Sodium Balance in Essential Hypertension

Is Renal β-Adrenergic-WNK4-NCC Pathway Important in Salt Hypertension of Dahl Rats?

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Regulation of Renal Na-K-Cl Cotransporter NKCC2 by Humoral Natriuretic Factors: Relevance in Hypertension

Cited by 10 publications

References 26 publications

Fluid secretion and the Na+-K+-2Cl− cotransporter in mouse exorbital lacrimal gland

Fluid secretion and the Na+-K+-2Cl− cotransporter in mouse exorbital lacrimal gland

Plasma Ouabain-Like Factor During Acute and Chronic Changes in Sodium Balance in Essential Hypertension

Is Renal β-Adrenergic-WNK4-NCC Pathway Important in Salt Hypertension of Dahl Rats?

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Product

Resources

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Fluid secretion and the Na⁺-K⁺-2Cl⁻ cotransporter in mouse exorbital lacrimal gland

Fluid secretion and the Na⁺-K⁺-2Cl⁻ cotransporter in mouse exorbital lacrimal gland