Cyclosporine reduces basolateral, but not apical, nitric oxide secretion in medullary thick ascending limb cells

Cyclosporine (CsA) reduces nitric oxide (NO) production in medullary thick ascending limb (mTAL) cells. We postulated that CsA affected NO secretion in a vectorial manner in polarized renal epithelial cells. The experiments were performed in a model of mTAL subcultured cells. The expression of iNOS in mTAL cells was confirmed by RT-PCR. The cells were grown on a non-permeable filter. Nitrite was measured by the modified Griess method. Transepithelial resistance was measured to ensure the integrity of the tight junction. CsA (100 ng/ml) reduced NO production by 22% in mTAL cells. The inhibitory effect was limited to the basolateral side (control: 165 ± 11; plus CsA: 93 ± 17 nM/10⁶ cells, P <0.001) without affecting apical NO secretion. The transepithelial resistance through the epithelial monolayer remained unchanged in CsA-treated cells. CsA reduced basolateral NO secretion without affecting apical secretion. The results suggest that CsA might affect intrarenal hemodynamics at the peritubular level.