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.
Soydan
Güray
G
Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Cekiç
Edip Güvenç
EG
Tuncer
Meral
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D004558:Electric Stimulation; D004983:Ethanolamines / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000098:blood supply* / Q000473:pathology / Q000502:physiology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology; D000068577:Nebivolol; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D004983:Ethanolamines; D014665:Vasodilator Agents; D000068577:Nebivolol; D000109:Acetylcholine