Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na and Cl permeabilities.

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 () and [Formula: see text]/[Formula: see text] in medullary thick ascending limbs. was 7,722 ± 1,554 ohm·cm in the control period and 6,318 ± 1,757 ohm·cm after l-arginine treatment ( < 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 ( < 0.04). Calculated [Formula: see text] and [Formula: see text] were 3.52 ± 0.2 and 1.81 ± 0.10 × 10 cm/s, respectively, in the control period. After l-arginine they were 6.65 ± 0.69 ( < 0.0001 vs. control) and 3.97 ± 0.44 ( < 0.0001) × 10 cm/s, respectively. NOS inhibition with -nitro-l-arginine methyl ester (5 mmol/l) prevented l-arginine's effect on Next we tested the effect of cGMP. 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 ( < 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 ( < 0.03). [Formula: see text] and [Formula: see text] were 4.58 ± 0.80 and 2.66 ± 0.57 × 10 cm/s, respectively, for the control period and 9.48 ± 1.63 ( < 0.007) and 6.01 ± 1.05 ( < 0.005) × 10 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.