Differential expression of pulmonary nitric oxide synthase isoforms after intestinal ischemia-reperfusion

Nitric oxide has been implicated in both attenuating and aggravating ischemia-reperfusion injury in most organs. This study aimed to investigate the role of nitric oxide produced by the two principal isoforms of nitric oxide synthase in the lung during post-ischemic reperfusion of the intestine.

Rats were randomized into four groups of 6 animals: Group A: laparotomy and superior mesenteric artery dissection without occlusion and maintenance for 2 h (control group at 2 h). Group B: laparatomy and superior mesenteric artery occlusion for 30 min and reperfusion of the intestine for 2 h (ischemia-reperfusion group at 2 h). Group C: control animals at 6 h. Group D: ischemia-reperfusion animals at 6 h. Arterial blood pressure was monitored throughout the procedure. Animals were euthanazed at the end of the experiment, and lungs were harvested for histological assessment of injury and for immunohistochemical examination of nitric oxide synthase isoforms and nitrotyrosine.

In all animals subjected to intestinal ischemia a period of systemic hypotension occurred immediately upon reperfusion. Histological evidence of lung injury was limited to those animals subjected to an intestinal reperfusion insult. Compared to control animals, pulmonary endothelial nitric oxide synthase expression was diminished at 2 h (p = 0.002), while expression of inducible nitric oxide synthase (p = 0.002) and nitrotyrosine (p = 0.02) was increased at 6 h.

Following intestinal ischemia-reperfusion, early pulmonary damage is associated with decreased endothelial nitric oxide synthase expression in the lung. Expression of inducible nitric oxide synthase occurs during the later stages of reperfusion; this leads to overproduction of nitric oxide with consequent nitrosylation of protein tyrosine residues and thus aggravated pulmonary injury.