Nitroglycerin and Iloprost Improve Mitochondrial Function in Colon Homogenate Without Altering the Barrier Integrity of Caco-2 Monolayers

Locally applied nitroglycerin [nitric oxide (NO) donor] and iloprost (analog of prostacyclin PGI(2)) improve regional gastric oxygenation and nitroglycerin preserves gastric mucosal barrier integrity. This suggests direct effects of these substances on oxygenation and barrier function. The aim of this study was to analyze the effect of iloprost and nitroglycerin on intestinal mitochondrial function and on mucosal barrier function in vitro. Mitochondrial oxygen consumption (respirometry) was determined in colon homogenates from 16 healthy rats before (baseline) and 15 min after incubation with nitroglycerin (25 and 250 μg/ml) and iloprost (0.1 and 1 μg/ml). State 2 (substrate-dependent oxygen consumption) and state 3 respiration (ADP-dependent oxygen consumption) were assessed and ADP/O ratio (ADP added/oxygen consumed) for complex I and II were calculated. For permeability measurement we used the Caco-2 monolayer. Fluorescein sulfonic acid (FS) (200 μg/ml) and the drugs were administered into the apical compartment of the transwell chamber. After 48 h, FS translocation was assessed as basolateral/apical FS. Both concentrations of nitroglycerin and iloprost reduced state 3 by stimulation via both complexes. Iloprost increased ADP/O ratio after stimulation via both complexes at both concentrations. Nitroglycerin increased ADP/O ratio at the higher concentration (250 μg/ml) after stimulation via complex I and at the lower concentration (25 μg/ml) via complex II. Neither nitroglycerin nor iloprost influenced FS translocation. Iloprost and nitroglycerin reduce the maximal mitochondrial respiration and improve the efficacy of oxidative phosphorylation in colon homogenates. Both drugs have no direct influence on mucosal barrier integrity of Caco-2 monolayers.