Plasma nitric oxide concentrations in broilers after intravenous injections of lipopolysaccharide or microparticles.
Nitric oxide is a potent vasodilator synthesized from l-Arg by NO synthase (NOS). Constitutive NOS in endothelial cells (eNOS) produces transient bursts of NO in low but physiologically effective levels. Activated monocytes and macrophages express inducible NOS (iNOS), which produces copious quantities of NO. Previous studies showed that NO attenuates pulmonary hypertensive responses induced by i.v. injections of lipopolysaccharide (LPS) or cellulose microparticles (MP). The present study determined whether changes in plasma NO concentrations could be used to assess the time course of NO production in response to LPS or MP injections. Broilers were injected i.v. with 1 mL of PBS (control), 1 mL of LPS (1 mg/mL), or 0.4 mL of MP (0.02 g/mL). Plasma samples were collected from 10 different broilers per group at 15, 30, 45, and 60 min and at 2, 3, 4, 5, 6, 8, 10, and 12 h postinjection. Total plasma NO concentrations were analyzed by nitrate + nitrite assay. After PBS or MP injection, plasma NO levels did not change throughout the 12-h period. Nitric oxide measured in the plasma increased in LPS-injected broilers from 4.8 +/- 0.8 microM at 15 min to 46.6 +/- 5.7 microM by 4 h postinjection, reached peak levels of 85.1 +/- 10.6 microM at 5 h, and returned to baseline levels similar to PBS-injected broilers by 12 h postinjection. We conclude that LPS triggered widespread iNOS expression by circulating monocytes and macrophages, resulting in copious NO production as reflected by significant increases in total plasma NO. Proportionally few monocytes and macrophages responded to MP entrapped in pulmonary arterioles. Consequently, NO produced by iNOS in activated leukocytes or by eNOS in the pulmonary vasculature had a minimal impact on total plasma NO. Total plasma NO from broilers did reflect the time course of massive iNOS activation in response to LPS, but biologically relevant quantities of NO produced by iNOS and eNOS activated during the local inflammatory response to entrapped MPs were too low to affect total plasma NO concentrations.
Bowen
O T
OT
Department of Poultry Science, University of Arkansas, Fayetteville 72701, USA. otbowen@uark.edu
Erf
G F
GF
Chapman
M E
ME
Wideman
R F
RF
D000818:Animals; D002482:Cellulose / Q000494:pharmacology*; D002645:Chickens / Q000378:metabolism*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D010316:Particle Size; D013997:Time Factors
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D002482:Cellulose