Apelin effects on lipopolysaccharide-increased pulmonary permeability in rats

Pretreatment with apelin-13 (AP-13, 2 mg/kg, i.p.), sodium butyrate (BUT, 200 mg/kg, s.c.) and N-acetyl-L-cysteine (NAC, 150 mg/kg, s.c.), all reduced the LPS-induced vascular leak measured as Evans blue extravasation, in rats lung tissue when compared to intranasal LPS (10 mg/100 mL) administered alone.

Although there is a significant difference either between AP-13 and BUT on one hand, and NAC and BUT on the other hand pretreatments, there is no significant difference between AP-13 and NAC pretreatments. Firstly, apelin-13 pretreatment might justify its effects through the modulation of endothelial layer functions. We recently demonstrated that AP-13 could diminish the endothelial dysfunction of pulmonary vein from both ovalbumin sensitized rats and rats with pulmonary hypertension. Furthermore, pretreatment with AP-13 + BUT, AP-13+NAC as well as BUT+ NAC reduced the LPS-induced vascular leak when compared to LPS alone. The reduction effects of BUT and NAC association were higher than those of either BUT or NAC alone. These synergistic effects might be associated to different and additive mechanisms of action of BUT and NAC. Thus, BUT might be primarily effective on macrophage migration and secondarily on activation and cytokine secretion by macrophages and NAC might be primarily effective on macrophages activation. Furthermore, since there are no significant effects between AP-13, NAC and AP-13+NAC we can conclude that AP-13 and NAC effects might be mediated through the same mechanisms (with the possible involvement of nuclear transcription factor NF-kB).