title: Synergism between leukocyte adherence and shear determines venular permeability in the presence of nitric oxide.
abstract: 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.
authors.affiliation: Department of Bioengineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zilberberg
authors.forename: N R
authors.initials: NR
authors.lastname: Harris
mesh_terms: 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*
chemical_list: D000911:Antibodies, Monoclonal; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester