title: Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na+and Cl-permeabilities.
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+([Formula: see text]) and Cl-([Formula: see text]) 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 [Formula: see text] and [Formula: see text] calculated from the transepithelial resistance (Rt) and [Formula: see text]/[Formula: see text] in medullary thick ascending limbs.Rtwas 7,722 ± 1,554 ohm·cm in the control period and 6,318 ± 1,757 ohm·cm after l-arginine treatment (P< 0.05). [Formula: see text]/[Formula: see text] was 2.0 ± 0.2 in the control period and 1.7 ± 0.1 after l-arginine (P< 0.04). Calculated [Formula: see text] and [Formula: see text] were 3.52 ± 0.2 and 1.81 ± 0.10 × 10-5cm/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) × 10-5cm/s, respectively. NOS inhibition withNω-nitro-l-arginine methyl ester (5 mmol/l) prevented l-arginine's effect onRtNext we tested the effect of cGMP.Rtin 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). [Formula: see text]/[Formula: see text] was 1.8 ± 0.1 in the control period and 1.6 ± 0.1 after db-cGMP (P< 0.03). [Formula: see text] and [Formula: see text] were 4.58 ± 0.80 and 2.66 ± 0.57 × 10-5cm/s, respectively, for the control period and 9.48 ± 1.63 (P< 0.007) and 6.01 ± 1.05 (P< 0.005) × 10-5cm/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.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio; casandra.monzon@case.edu.|Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales-Universidad de Buenos Aires, Buenos Aires, Argentina; and.
authors.forename: Casandra M
authors.initials: CM
authors.lastname: Monzon
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Rossana
authors.initials: R
authors.lastname: Occhipinti
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales-Universidad de Buenos Aires, Buenos Aires, Argentina; and.|Laboratorio de Endocrinología Molecular y Transducción de Señales, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: Omar P
authors.initials: OP
authors.lastname: Pignataro
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Garvin
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism*; D006152:Cyclic GMP / Q000494:pharmacology; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010477:Perfusion; D010539:Permeability; D017207:Rats, Sprague-Dawley; D065608:Renal Reabsorption / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*
chemical_list: D002712:Chlorides; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester
keywords: kidney; nitric oxide; paracellular permeability; sodium transport