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Abstract:

About 50% of the Na+ reabsorbed in thick ascending limbs traverses the paracellular pathway. Nitric oxide (NO) reduces the permselectivity of this pathway via cGMP, but its effects on absolute Na+ (PNa +) and Cl- (PCl -) permeabilities are unknown. To address this, we measured the effect of L-arginine (0.5 mmol/l; NO synthase substrate) and cGMP (0.5 mmol/l) on PNa + and PCl - calculated from the transepithelial resistance (Rt) and PNa +/PCl - in medullary thick ascending limbs. Rt was 7,722 ± 1,554 ohm·cm in the control period and 6,318 ± 1,757 ohm·cm after L-arginine treatment (P < 0.05). PNa +/PCl - was 2.0 ± 0.2 in the control period and 1.7 ± 0.1 after L-arginine (P < 0.04). Calculated PNa + and PCl - were 3.52 ± 0.2 and 1.81 ± 0.10 × 10-5 cm/s, respectively, in the control period. After L-arginine they were 6.65 ± 0.69 (P < 0.0001 vs. control) and 3.97 ± 0.44 (P < 0.0001) × 10-5 cm/s, respectively. NOS inhibition with Nω-nitro-L-arginine methyl ester (5 mmol/l) prevented L-arginine’s effect on Rt. Next we tested the effect of cGMP. Rt in the control period was 7,592 ± 1,470 and 4,796 ± 847 ohm·cm after dibutyryl-cGMP (0.5 mmol/l; db-cGMP) treatment (P < 0.04). PNa +/PCl - was 1.8 ± 0.1 in the control period and 1.6 ± 0.1 after db-cGMP (P < 0.03). PNa + and PCl - were 4.58 ± 0.80 and 2.66 ± 0.57 × 10-5 cm/s, respectively, for the control period and 9.48 ± 1.63 (P < 0.007) and 6.01 ± 1.05 (P < 0.005) × 10-5 cm/s, respectively, after db-cGMP. We modeled NO’s effect on luminal Na+ concentration along the thick ascending limb. We found that NO’s effect on the paracellular pathway reduces net Na+ reabsorption and that the magnitude of this effect is similar to that due to NO’s inhibition of transcellular transport. © 2017 the American Physiological Society.

Registro:

Documento: Artículo
Título:Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na+ and Cl- permeabilities
Autor:Monzon, C.M.; Occhipinti, R.; Pignataro, O.P.; Garvin, J.L.
Filiación:Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States
Departamento de Química Biológica, Facultad de Ciencias Exactas Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Laboratorio de Endocrinología Molecular y Transducción de Señales, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
Palabras clave:Kidney; Nitric oxide; Paracellular permeability; Sodium transport; chloride; nitric oxide; sodium; arginine; chloride; cyclic GMP; enzyme inhibitor; n(g) nitroarginine methyl ester; nitric oxide; nitric oxide synthase; sodium; animal experiment; Article; cell membrane permeability; conductance; controlled study; electric potential; limb; male; Michaelis Menten kinetics; nonhuman; osmolality; priority journal; rat; steady state; transcytosis; transepithelial resistance; velocity; animal; antagonists and inhibitors; biological model; drug effects; Henle loop; impedance; in vitro study; kidney tubule absorption; metabolism; perfusion; permeability; Sprague Dawley rat; transport at the cellular level; Animals; Arginine; Biological Transport; Chlorides; Cyclic GMP; Electric Impedance; Enzyme Inhibitors; In Vitro Techniques; Loop of Henle; Male; Models, Biological; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Perfusion; Permeability; Rats, Sprague-Dawley; Renal Reabsorption; Sodium
Año:2017
Volumen:312
Número:6
Página de inicio:F1035
Página de fin:F1043
DOI: http://dx.doi.org/10.1152/ajprenal.00671.2016
Título revista:American Journal of Physiology - Renal Physiology
Título revista abreviado:Am. J. Physiol. Renal Physiol.
ISSN:03636127
CODEN:AJPPF
CAS:chloride, 16887-00-6; nitric oxide, 10102-43-9; sodium, 7440-23-5; arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; cyclic GMP, 7665-99-8; n(g) nitroarginine methyl ester, 50903-99-6; nitric oxide synthase, 125978-95-2; Arginine; Chlorides; Cyclic GMP; Enzyme Inhibitors; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Sodium
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03636127_v312_n6_pF1035_Monzon

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Citas:

---------- APA ----------
Monzon, C.M., Occhipinti, R., Pignataro, O.P. & Garvin, J.L. (2017) . Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na+ and Cl- permeabilities. American Journal of Physiology - Renal Physiology, 312(6), F1035-F1043.
http://dx.doi.org/10.1152/ajprenal.00671.2016
---------- CHICAGO ----------
Monzon, C.M., Occhipinti, R., Pignataro, O.P., Garvin, J.L. "Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na+ and Cl- permeabilities" . American Journal of Physiology - Renal Physiology 312, no. 6 (2017) : F1035-F1043.
http://dx.doi.org/10.1152/ajprenal.00671.2016
---------- MLA ----------
Monzon, C.M., Occhipinti, R., Pignataro, O.P., Garvin, J.L. "Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na+ and Cl- permeabilities" . American Journal of Physiology - Renal Physiology, vol. 312, no. 6, 2017, pp. F1035-F1043.
http://dx.doi.org/10.1152/ajprenal.00671.2016
---------- VANCOUVER ----------
Monzon, C.M., Occhipinti, R., Pignataro, O.P., Garvin, J.L. Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na+ and Cl- permeabilities. Am. J. Physiol. Renal Physiol. 2017;312(6):F1035-F1043.
http://dx.doi.org/10.1152/ajprenal.00671.2016