Endogenous production of nitric oxide in endotoxemic piglets.
We sought to assess the relation between endotoxin-induced pulmonary hypertension and the production of nitric oxide (NO) in neonatal animals. Adult animals respond to endotoxin by increasing exhaled NO and plasma NO metabolites. The response of neonatal animals has not previously been reported. We administered 20 microg/kg of Escherichia coli lipopolysaccharide (LPS) to 12- to 18-day-old and to 5- to 7-week-old piglets. Pulmonary vascular resistance increased significantly in both age groups. Exhaled NO in the 12- to 18-day-old animals and in the 5- to 7-week-old piglets did not increase significantly. A similarly treated group of adult rats did show a significant increase in exhaled NO (2.6 +/- 1.0 to 109.5 +/- 54.3 ppb; p = 0.028). Plasma NO metabolite measurements followed the same pattern of no increase in both porcine groups, and a large increase in the rat group. However, immunostaining of lungs from 12- to 18-day-old piglets did reveal an increase in inducible NO synthase. These results suggest that piglets demonstrate a limited ability to modulate LPS-induced pulmonary hypertension by elevations in exhaled NO. They also demonstrate the differential response to LPS between species.
Kaftan
Harold A
HA
Section of Neonatology, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri, 2401 Gillham Road, Kansas City, MO 64108, USA.
Clark
Perry L
PL
Norberg
Mike
M
Garg
Uttam
U
Thibeault
Donald W
DW
Truog
William E
WE
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D019446:Endotoxemia / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat