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- W2073504384 abstract "Intestinal ischemia-reperfusion (I/R) causes pulmonary microvascular dysfunction which, at least in part, is due to oxidant-mediated endothelial injury. Previous studies in our laboratory using cultured pulmonary microvascular endothelial cells have shown that insulin attenuates peroxide-induced barrier dysfunction via a nitric oxide (NO)-dependent mechanism. This study examines the hypothesis that insulin prevents I/R-induced pulmonary microvascular barrier dysfunction by a mechanism dependent upon the presence of NO. Male C57/BL6 mice underwent occlusion of the superior mesenteric artery (SMA) for 60 minutes followed by 120 minutes of reperfusion (I/R) or dissection of the SMA without occlusion (SHAM). The animals received vehicle, insulin (0.1 units/kg, 30 min. prior to ischemia) or insulin + L-NAME (100 mM, a NO synthase inhibitor, 60 min. prior to ischemia) intravenously. Pulmonary microvascular dysfunction was quantitated by measuring the concentration of Evans Blue Dye (EBD) within the lung following the intravenous administration of 20 mg/kg EBD. Statistical significance was determined using a one-way ANOVA with a Bonferroni post-hoc test. The concentration of EBD within the lungs of mice undergoing I/R was nearly twice that of SHAM operated animals (p < 0.01, SHAM vs. I/R); this effect was prevented by the administration of insulin (p < 0.05, I/R + insulin vs. I/R). Inhibition of NOS with L-NAME abolished insulin’s beneficial effect (p < 0.05, I/R + insulin vs. I/R + insulin + L-NAME). In the absence of I/R, insulin or L-NAME alone had no effect on pulmonary EBD concentration (data not shown). Intestinal I/R causes pulmonary microvascular barrier dysfunction which is prevented by insulin pretreatment. As in our in vitro studies on oxidant-stressed endothelial cells, this protective effect was dependent upon the activity of nitric oxide synthase. These data suggest that insulin’s protective effect on endothelial barrier function during pro-inflammatory states is related to insulin’s known stimulatory effect on endothelial nitric oxide release." @default.
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- W2073504384 date "2006-02-01" @default.
- W2073504384 modified "2023-09-28" @default.
- W2073504384 title "Insulin attenuates intestinal I R mediated pulmonary injury via a no dependent mechanism" @default.
- W2073504384 doi "https://doi.org/10.1016/j.jss.2005.11.148" @default.
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