title: Postischemic endothelium-dependent vascular reactivity is preserved in adhesion molecule-deficient mice.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Banda
authors.forename: D J
authors.initials: DJ
authors.lastname: Lefer
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018845:CD11 Antigens / Q000235:genetics / Q000502:physiology; D018821:CD18 Antigens / Q000235:genetics / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology*; D014664:Vasodilation
chemical_list: D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D009599:Nitroprusside; D000109:Acetylcholine