1. Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and
inflammation which contribute to the pathophysiology of
shock. We investigated the effects of
relaxin (RLX), known to afford protection against the deleterious effects of cardiac
ischemia/reperfusion, given to rats subjected to splanchnic artery occlusion and reperfusion (SAO/R)-induced splanchnic injury. 2. RLX (30 ng kg(-1), 15 min. before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/R. RLX also reduced histopathological changes, leukocyte infiltration (
myeloperoxidase) and expression of endothelial cell adhesion molecules in the ileum. RLX counteracted
free radical-mediated tissue injury, as judged by significant decrease in the tissue levels of peroxidation and nitration products (
malondialdehyde,
nitrotyrosine), DNA damage markers (8-hydroxy-2'-deoxyguanosine, poly-ADP-ribosylated DNA) and consumption of tissue
antioxidant enzymes (
superoxide dismutase). As a result, RLX led to a reduction of ileal cell apoptosis (
caspase 3, terminal
deoxynucleotidyltransferase-mediated
UTP end labeling). The effects of RLX appear specific, as inactivated RLX substituted for the bioactive
hormone had no effects. 3. In conclusion, these results show that RLX exerts a clear-cut protective effect in SAO/R-induced splanchnic injury, likely due to endothelial protection, decreased leukocyte recruitment and hindrance of
free radical-mediated tissue injury leading to cell death, lethal complications and high mortality rate. Thus, RLX could be used therapeutically in intestinal
ischemia.