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+ (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 x 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) x 10–5 cm/s, respectively. NOS inhibition with N-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 &plu...

Source: AJP: Renal Physiology - June 1, 2017 Category: Urology & Nephrology Authors: Monzon, C. M., Occhipinti, R., Pignataro, O. P., Garvin, J. L. Tags: RESEARCH ARTICLE Source Type: research