Postischemic endothelium-dependent vascular reactivity is preserved in adhesion molecule-deficient mice.

Previous studies utilizing monoclonal antibodies directed against specific leukocyte-endothelial cell adhesion proteins have suggested that neutrophils mediate endothelial cell injury in a number of vascular beds after ischemia-reperfusion (I/R). In the present study, we investigated superior mesenteric artery (SMA) vascular reactivity to acetylcholine (ACh) and sodium nitroprusside (SNP) after occlusion and reperfusion in wild-type (C57BL/6) mice and in gene-targeted mice that are deficient in either CD11/CD18, intercellular adhesion molecule 1 (ICAM-1), or P-selectin. All mice were 4 wk of age, and the SMA was occluded for 45 min and then reperfused for 45 min. Segments of SMA were isolated and suspended in organ chambers and contracted with phenylephrine (10-5 M), and the maximal vasorelaxation to ACh (10-6 M) and SNP (10-6 M) was measured. SMA from sham-operated C57BL/6 mice relaxed 83.5 ± 3.3% to ACh and 91.7 ± 3.4% to SNP. In contrast, segments of SMA from C57BL/6 mice subjected to I/R demonstrated a marked impairment in vasorelaxation to ACh (51.3 ± 4.7%, P < 0.01 vs. sham) without any impairment in the vasoreactivity to SNP (86.1 ± 5.5%). In CD11/CD18-deficient mice, SMA reactivity to ACh (84.7 ± 2.3%) and SNP (91.2 ± 2.8%) was unaffected by I/R. Similarly, SMA rings from ICAM-1-deficient mice exhibited normal vasorelaxation to ACh and SNP with maximal vasorelaxation of 83.1 ± 2.9 and 87.4 ± 3.0%, respectively. We also observed profound preservation of endothelium-dependent vasorelaxation after I/R in P-selectin-deficient mice. These findings indicate that leukocyte-endothelial cell adhesion molecule deficiency is associated with the preservation of endothelium-dependent vascular responses after I/R.