Ketamine/Xylazine attenuates LPS-induced iNOS expression in various rat tissues

Ketamine and xylazine (K/X) are commonly used in combination as an anesthetic agent in experimental animal models. We previously noted that K/X attenuated lipopolysaccharide (LPS)-induced liver injury, gastric stasis, and reduced symptoms of endotoxemia. Because ketamine attenuates expression of several proinflammatory genes, we examined the effects of K/X on inducible nitric oxide synthase (iNOS), which has been implicated in endotoxin-induced tissue injury. We hypothesized that K/X would attenuate LPS-induced expression of iNOS in various organs in the rat. Rats were given either intraperitoneal saline or ketamine (70 mg/kg) and xylazine (6 mg/kg) 1 h before saline or LPS (20 mg/kg). Rats were sacrificed 5 h later and stomach, duodenum, jejunum, ileum, colon, liver, lung, kidney, and spleen were collected for determination of iNOS protein immunoreactivity by Western immunoblot. Data reported in densitometric units (DU) as mean ± SEM (n ≥ 5; ANOVA). LPS significantly increased iNOS protein immunoreactivity in all tissues examined versus saline controls (P ≤ 0.05, all groups). K/X significantly attenuated LPS-induced iNOS protein immunoreactivity in all of the aforementioned organs (P ≤ 0.05, all groups). Furthermore, K/X almost completely blunted LPS-induced expression of iNOS in stomach, duodenum, jejunum, and colon. These data indicate that K/X attenuates LPS-induced upregulation of iNOS in a variety of tissues. Furthermore, in rat models studying the in vivo effects of endotoxin, especially those evaluating the gastrointestinal system, careful consideration needs to be given if the anesthetic combination of K/X is used, as it alters LPS-induced expression of iNOS, an important pathophysiologic mediator in endotoxemia.