The anti-inflammatory role of nitric oxide (NO) was studied in a model of hepatic ischemia-reperfusion (I/R) in rats. Male Fischer rats were subjected to 30 min of no-flow ischemia of the left and median lobes of the liver, and animals were examined for a 4-h period of reperfusion. The animals were divided into the following groups: control-vehicle; I/R-vehicle; I/R- N ω-nitro-l-arginine methyl ester (l-NAME, 10 mg/kg iv, 10 min before reperfusion); sham control-l-NAME, and I/R- S-nitroso- N-acetyl-penicillamine (SNAP, 25 μmol/kg iv, 10 min before reperfusion, followed by 20 μmol ⋅ kg−1 ⋅ h−1in 1.0 ml saline infused for 4 h). Results showed that mean arterial blood pressure was significantly increased in the sham control-l-NAME or I/R-l-NAME groups compared with either the I/R-vehicle or I/R-SNAP groups. However, cardiac index (CI) and stroke volume index (SVI) were markedly decreased, and systemic vascular resistance index (SVRI) was dramatically increased. Interestingly, the CI and SVI in rats treated with SNAP were markedly improved over that of the I/R group. Plasma nitrate and nitrite levels were significantly decreased in the I/R-l-NAME group; however, superoxide generation in the ischemic lobes and plasma alanine aminotransferase activity were higher compared with I/R-SNAP rats. Thel-NAME-induced enhancement of hepatic injury in rats with I/R may be due in part to neutrophil infiltration, which was significantly increased compared with animals subjected to I/R or I/R-SNAP. The mechanism ofl-NAME-enhanced neutrophil infiltration may be due to the fact that the ratios of P-selectin and intercellular adhesion molecule 1 (ICAM-1) mRNA to glyceraldehyde-3-phosphate dehydrogenase mRNA extracted from the ischemic lobes of I/R-l-NAME rats were significantly increased when compared with the I/R-SNAP group. These results suggest that 1) endogenous NO reduces the SVRI and permits an increased CI and SVI; 2) exogenous NO further improves CI and SVI; and 3) endogenous, but not exogenous, NO decreases P-selectin and ICAM-1 mRNA expression, thereby reducing polymorphonuclear neutrophil-dependent reperfusion tissue injury.

No abstract

MI/R is associated with an increase in circulating leukocytes and generation of superoxide in the peri-ischemic areas of the heart of young rats, compared to aged rats. However, MI/R induces a significant decrease in cardiac index and stroke volume index in aged rats, when compared to young rats following MI/R. Furthermore, aged rats exhibit an increase in the ratio of Bax mRNA to Bcl-2 mRNA and cardiomyocyte apoptosis following MI/R, which may explain, at least in part, the enhanced myocardial dysfunction.