NO modulates P-selectin and ICAM-1 mRNA expression and hemodynamic alterations in hepatic I/R

Abstract

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.

Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats

“…Captopril or losartan treatment did not affect the increase in angiotensinogen caused by ischemia and reperfusion. As has been observed by others, 19,20 expression of ICAM-1 and TNF␣ in rat liver was increased 3 hours after reper- Fig. 1.…”

C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression

“…Thus, we wished to obtain insight into which NPR was involved in mediating CNP-induced inhibition of leukocyte rolling. In this regard, we used the selective NPR-C agonist (17), cANF [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] (because of the lack of availability of selective NPR-B antagonists). cANF [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] mimicked the inhibitory actions of CNP on leukocyte recruitment; although this observation only provides circumstantial evidence that CNP exerts its antileukocyte effects via this NPR, it does demonstrate that NPR-C activation is functionally important in the regulation of leukocyte-endothelial cell interactions.…”

“…CNP (0.1-1 M) was superfused for 10 min, and leukocyte flux was recorded. To investigate the involvement of the NPR-C in responses to CNP, the ability of the selective NPR-C agonist (17), cANF [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] (1 M) to inhibit leukocyte rolling was also explored.…”

Influence of nitric oxide on microcirculation in pancreatic ischemia/reperfusion injury: an intravital microscopic study

“…In kidneys higher lipid-peroxidation [21] after administrating L-arginine could have a toxic effect on tubular cells [22] but publications also see a protective effect of L-arginine and sodium nitroprusside [23], e.g. in the liver [24]. In the heart protective effects are described both for nitric oxide administration and inhibition of nitric oxide-synthesis [25] but also direct toxic effects of L-arginine on cardiomyocytes were seen [26].…”