Ashish Khanna1, Jon Rossman, Michael G Caty, Ho Leung Fung. 1. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York 14260, USA. hlfung@buffalo.edu
Abstract
BACKGROUND: We examined the effects of intraluminal nitroglycerin (NTG) on various physiologic functions and intestinal pathology in intestinal ischemia-reperfusion (IR) injury in rats. MATERIAL AND METHODS: Intraluminal NTG (0.15-3.75 mg/kg) was administered at different doses and stages during the experimental disease, and intestinal permeability and histology, bile flow, and systemic hemodynamics were measured. RESULTS: Prophylactic intraluminal NTG treatment at 0.75 mg/kg, but not at 0.15 mg/kg, significantly attenuated the deleterious changes in intestinal barrier function and mucosal injury caused by IR. However, administration of NTG after ischemia was not effective, even up to 3.75 mg/kg. In vitro intestinal NTG metabolism was significantly decreased following intestinal ischemia. Intraluminal NTG at 0.75 mg/kg significantly attenuated the reduction in bile flow that accompanied IR. Reperfusion induced a precipitous and sustained decrease in mean arterial pressure, which was blunted by intraluminal NTG. CONCLUSIONS: Intraluminal NTG produced several beneficial local and systemic effects in a rat model of intestinal IR. In this disease model, 0.75 mg/kg intraluminal NTG did not exacerbate, but rather reduced, the hypotensive effects induced by IR.
BACKGROUND: We examined the effects of intraluminal nitroglycerin (NTG) on various physiologic functions and intestinal pathology in intestinal ischemia-reperfusion (IR) injury in rats. MATERIAL AND METHODS: Intraluminal NTG (0.15-3.75 mg/kg) was administered at different doses and stages during the experimental disease, and intestinal permeability and histology, bile flow, and systemic hemodynamics were measured. RESULTS: Prophylactic intraluminal NTG treatment at 0.75 mg/kg, but not at 0.15 mg/kg, significantly attenuated the deleterious changes in intestinal barrier function and mucosal injury caused by IR. However, administration of NTG after ischemia was not effective, even up to 3.75 mg/kg. In vitro intestinal NTG metabolism was significantly decreased following intestinal ischemia. Intraluminal NTG at 0.75 mg/kg significantly attenuated the reduction in bile flow that accompanied IR. Reperfusion induced a precipitous and sustained decrease in mean arterial pressure, which was blunted by intraluminal NTG. CONCLUSIONS: Intraluminal NTG produced several beneficial local and systemic effects in a rat model of intestinal IR. In this disease model, 0.75 mg/kg intraluminal NTG did not exacerbate, but rather reduced, the hypotensive effects induced by IR.
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