Effects of L-NA and sodium nitroprusside on ischemia/reperfusion-induced leukocyte adhesion and macromolecular leakage in hamster cheek pouch venules

Our objective was to study how the topical application of a nitric oxide sy nthase inhibitor (L-NA, N omega -nitro-L-arginine) and a nitric oxide donor , sodium nitroprusside (SNP), could modulate leukocyte adhesion (sticking) and microvascular permeability as altered by ischemia/reperfusion (I/R) and topically applied histamine after I/R. Golden hamsters were prepared for i ntravital microscopy. Ischemia was induced by an inflatable silicon rubber cuff mounted around the neck of the cheek pouch prepared for intravital mic roscopy. Saline, L-NA, sodium nitroprusside, and histamine were applied in the superfusion solution. FITC-dextran was injected iv 30 min before initia tion of ischemia as a marker of microvascular permeability. L-NA 10(-5) M i nhibited both the increase in number of sticking leukocytes and the increas e in vascular permeability after I/R compared with the untreated control gr oup of hamsters. SNP neutralized this effect of L-NA on leukocytes and vasc ular permeability and caused arteriolar dilation at the concentration used, 10(-6) M. Both SNP and L-NA + SNP enhanced the I/R-induced macromolecular leakage. The topical application of SNP and SNP + L-NA did not modify the r esponse to histamine after I/R compared with the untreated control group. I n hamsters not subjected to I/R, histamine-induced macromolecular leakage w as inhibited by L-NA and L-NA + SNP but was unchanged by SNP. It is conclud ed that inhibition of nitric oxide formation by L-NA reduced both leukocyte adhesion in postcapillary venules and the increase in macromolecular leaka ge and that a NO donor such as SNP could enhance the macromolecular leakage response to I/R. (C) 2001 Academic Press.