Nebivolol has Protective Effect Against Endothelial and Ileal Dysfunction due to I/R

In this study, two enantiomers of the drug, L-nebivolol and racemic nebivolol, were used to measure and compare their ability to prevent endothelial dysfunction, disturbed ileal contractility, and ileal injury induced by I/R.The superior mesenteric artery of male Sprague-Dawley rats was occluded for 45 min to induce ischemia, and then the clamp was removed for 60-min reperfusion. Drugs or saline were administered prior to the surgical procedure in the I/R and sham-operated groups. Vasodilation in the third branch of the mesenteric artery was evaluated with a myograph system. Isometric contractions of the ileal segments in response to acetylcholine or electrical field stimulation (EFS) (120 V, 2-ms pulse duration for 5 s, 1–20 Hz) were recorded on a polygraph. Additionally, the ileal segments were examined histopathologically.Acetylcholine-induced relaxation of the mesenteric artery, precontracted by submaximal phenylephrine, markedly decreased after I/R. L-nebivolol pretreatment reversed this relaxation, but racemic nebivolol did not. Contractions induced by both acetylcholine and EFS were significantly reduced after I/R. L-nebivolol, but not racemic nebivolol, prevented this reduction in the acetylcholine-induced contractions. I/R-induced reduction was prevented by L-nebivolol only in response to EFS of 20 Hz. Intestinal I/R caused severe ischemic injury in the rat ileum, which was prevented by L-nebivolol, but not racemic nebivolol. Control responses were not affected by L-nebivolol or racemic nebivolol.These results suggest that L-nebivolol had a protective effect against both endothelial dysfunction of the mesenteric artery and ileal injury induced by intestinal I/R; however, similar effects were not observed for racemic nebivolol.