Abstract
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/10(6) 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.
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