Synergism between leukocyte adherence and shear determines venular permeability in the presence of nitric oxide.
The effects of nitric oxide (NO) on vascular permeability tend to be controversial. While many studies indicate that NO plays a protective role in several models of inflammation by reducing leukocyte-endothelial cell adhesion, in vitro studies have shown that endothelial permeability to macromolecules increases with increasing shear forces via a NO-dependent mechanism. Most investigations of the role of shear on endothelial permeability have been performed either in vitro or in cannulated vessels, but whether NO and leukocyte adherence (WBC-adh) mediate shear-induced control of albumin leakage in autoperfused venules has yet to be determined. By measuring permeability under regular conditions of blood flow and WBC-adh, we recently found that venular albumin permeability of the rat mesentery correlates strongly with basal levels of both shear rate and WBC-adh. Using the same model in the present study, we were able to further elucidate some of the mechanisms and mediators of venular permeability. In one set of experiments, a role for NO in shear-mediated permeability was confirmed. In additional experiments, a permeability-enhancing collaboration between shear and WBC-adh was revealed: shear-induced permeability was found to be dependent on the presence of adherent leukocytes, and similarly, leukocyte-mediated permeability was found to be dependent on shear. This synergism was present both under basal conditions and following the inflammatory stimulus of ischemia-reperfusion.
Zilberberg
J
J
Department of Bioengineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Harris
N R
NR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D002199:Capillary Permeability / Q000502:physiology*; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D018715:Microscopy, Video / Q000295:instrumentation / Q000379:methods; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000502:physiology; D013314:Stress, Mechanical; D014699:Venules / Q000502:physiology*
D000911:Antibodies, Monoclonal; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester