Nitric Oxide Mediates Lung Injury Induced by Ischemia-Reperfusion in Rats

Abstract

Nitric oxide (NO) has been reported to play a role in lung injury (LI) induced by ischemia-reperfusion (I/R). However, controversy exists as to the potential beneficial or detrimental effect of NO. In the present study, an in situ, perfused rat lung model was used to study the possible role of NO in the LI induced by I/R. The filtration coefficient (K_fc), lung weight gain (LWG), protein concentration in the bronchoalveolar lavage (PCBAL), and pulmonary arterial pressure (PAP) were measured to evaluate the degree of pulmonary hypertension and LI. I/R resulted in increased K_fc, LWG, and PCBAL. These changes were exacerbated by inhalation of NO (20–30 ppm) or 4 mML-arginine, an NO precursor. The permeability increase and LI caused by I/R could be blocked by exposure to 5 mM N^ω-nitro-L-arginine methyl ester (L-NAME; a nonspecific NO synthase inhibitor), and this protective effect of L-NAME was reversed with NO inhalation.Inhaled NO prevented the increase in PAP caused by I/R, while L-arginine had no such effect. L-NAME tended to diminish the I/R-induced elevation in PAP, but the suppression was not statistically significant when compared to the values in the I/R group.These results indicate that I/R increases K_fc and promotes alveolar edema by stimulating endogenous NO synthesis. Exogenous NO, either generated from L-arginine or delivered into the airway, is apparently also injurious to the lung following I/R.

The Effect of Nω-Nitro-l-Arginine Methyl Ester and l-Arginine on Lung Injury Induced by Abdominal Aortic Occlusion–Reperfusion

“…39 Kao et al found that exogenous NO, generated from l-arginine, increased the extent of IR-induced lung injury in a perfused rat lung model. 40 We also found the MDA level to further increase in the l-arginine+aortic IR group. During IR-induced lung injury, neutrophil adherence to the endothelium is a prerequisite of PMN migration through the vascular wall and subsequent infi ltration into alveoli and interstitial space.…”

Insulin attenuates endotoxin-induced acute lung injury in conscious rats

“…We used an equation for the estimation of the initial LW in relation to BW (19). Both LW and BW were obtained from 30 rats killed by decapitation.…”

“…Lavage samples were centrifuged at 1500 ϫ g at room temperature for 10 mins. The PCBAL in the supernatant was determined with a spectrophotometer by measuring the change in absorbance at 630 nm after the addition of bromocresol green (19).…”

The detrimental role of inducible nitric oxide synthase in the pulmonary edema caused by hypercalcemia in conscious rats and isolated lungs

“…Although the role of iNOS-NO pathway in acute lung injury is still a subject for debate [1,2,36], accumulating evidence using iNOS-knockout mice and specific iNOS inhibitors suggests that NO production through the iNOS system play a detrimental role in lung injury caused by endotoxemia, carrageenan exposure, hyperoxia, bleomycin administration, ischemia/reperfusion and other etiologies [37][38][39][40]. Our laboratory reported that NO production in the lung through the iNOS system caused lung injury in septic rats [10].…”