Inhaled nitric oxide modulates leukocyte kinetics in the mesenteric venules of endotoxemic rats.
OBJECTIVE
to determine whether inhaled nitric oxide (NO) would alter leukocyte kinetics in the septic microvasculature.


METHODS
Randomized, controlled trial.


METHODS
Experimental laboratory.


METHODS
Male Sprague Dawley rats.


METHODS
Rats were treated with either saline or endotoxin (10 mg/kg, iv) and then allowed to breathe either air or air plus NO (10 ppm).


RESULTS
After a 4-hr period, rolling, firm adhesion, and emigration of leukocytes and endothelial dysfunction were monitored in mesenteric venules by using intravital videomicroscopy. Compared with controls, endotoxemic rats exhibited a profound influx in mesenteric venule rolling leukocytes (55+/-17 vs. 70+/-19 leukocytes/min; p < .05), associated with a reduction of leukocyte rolling velocity (83+/-14 vs. 34+/-3 microm/sec; p < .05). In endotoxemic rats, venular endothelium leukocyte firm adhesion (1.15+/-0.32 vs. 4.08+/-0.96 leukocytes/ 100 microm; p < .05) and emigration (0.84+/-0.47 vs. 4.23+/-1.2 leukocytes/100 microm; p < .05) increased compared with controls. Inhaled NO had no effect on leukocyte kinetics in control rats. Inhaled NO significantly attenuated endotoxin-induced venular endothelium leukocyte adhesion (4.08+/-0.96 vs. 1.86+/-0.76 leukocytes/100 microm; p < .05) and emigration (4.23+/-1.2 vs. 1.68+/-0.72 leukocytes/100 microm; p < .05). Compared with control rats, macromolecular (FITC-dextran) vascular leakage, expressed as the perivenular/intravenular fluorescence intensity ratio, increased in endotoxemic rats (0.56+/-0.02 vs. 0.81+/-0.05; p < .01). Endotoxin-induced macromolecular vascular leakage increases were partially prevented by inhaled NO (0.66+/-0.01 vs. 0.56+/-0.02; p < .05).


CONCLUSIONS
These observations suggest that inhaled NO reduces leukocyte adhesion and the degree of vascular permeability dysfunction in mesenteric venule of endotoxemic rats.
Nevière
R
R
Service de Réanimation Médicale, Hopital R. Salengro, France.
Mordon
S
S
Maréchal
X
X
Buys
B
B
Guery
B
B
Mathieu
D
D
Wattel
F
F
Chopin
C
C
D000280:Administration, Inhalation; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects* / Q000503:physiopathology; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D014699:Venules / Q000187:drug effects / Q000503:physiopathology
D014665:Vasodilator Agents; D009569:Nitric Oxide