The role of nitric oxide and cell adhesion molecules on the microcirculation in ischaemia-reperfusion.
The microcirculation undergoes a profound degree of endothelial dysfunction within minutes (i.e., 2.5 to 5 min) following reperfusion of ischaemic vasculature. This has been documented in the coronary and mesenteric microcirculation. The endothelial dysfunction is characterized by a loss in basal and agonist-mediated nitric oxide (NO) produced by the vascular endothelium. The loss of NO results in upregulation of cell adhesion molecules (CAMs) particularly P-selectin 10-20 min following reperfusion. Thus, CAM upregulation renders the endothelium sticky, and a marked degree of leukocyte adherence (particularly neutrophils) occurs 20 min following reperfusion. This enhanced involvement of neutrophils leads to neutrophil infiltration into the underlying tissue (e.g., myocardium) within 2-3 h of reperfusion. The infiltration of neutrophils leads to reperfusion injury (i.e., necrosis) which is significant at 3 h but becomes profound at 4.5 h following reperfusion. Cardiac necrosis can be significantly attenuated by treatment with NO, an organic NO donor, L-arginine, or specific blockers of CAMs given just prior to reperfusion. This approach is a promising one for a variety of types of reperfusion injury.
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
A M
AM
Lefer
D J
DJ
Lefer
D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D008833:Microcirculation / Q000502:physiology*; D018375:Neutrophil Activation / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D015427:Reperfusion Injury / Q000209:etiology*
D015815:Cell Adhesion Molecules; D009569:Nitric Oxide