Hypotension during septic shock does not correlate with plasma levels of nitric oxide metabolites in the conscious rat.
Hypotension following administration of lipopolysaccharide may be due to excessive production of the potent vasodilator nitric oxide brought about by induction of nitric oxide synthase. The purpose of this study was to determine in conscious, fasted rats what role nitric oxide played in lipopolysaccharide-induced hypotension. When examined by Western immunoblot analysis, inducible nitric oxide synthase immunoreactivity was detected in the aorta at 3 hours and increased over time following administration of intraperitoneal lipopolysaccharide (20 mg/kg). When compared with saline-treated control rats, significant hypotension was observed at 2, 4, and 6 hours following lipopolysaccharide treatment. Blood pressure at 2 hours did not differ significantly from that at 6 hours. Using the Griess reaction to quantify plasma levels of nitrates and nitrites as an index of systemic nitric oxide production, an augmentation in the formation of these nitric oxide metabolites was demonstrated at 4 and 6 hours but not at 2 hours. Subcutaneous administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (5 mg/kg) prevented lipopolysaccharide-induced hypotension, an effect reversed by subcutaneous L-arginine but not D-arginine (350 mg/kg). However, nitric oxide synthase inhibition did not attenuate the ability of lipopolysaccharide to increase plasma nitrate/nitrite levels. These data indicate that lipopolysaccharide-induced production of nitric oxide metabolites does not correlate with lipopolysaccharide-induced hypotension.
Klemm
K
K
Department of Surgery, University of Texas-Houston Medical School, Houston, Tex, USA.
Mercer
D W
DW
Mailman
D
D
Moody
F G
FG
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D007022:Hypotension / Q000097:blood* / Q000150:complications; D008070:Lipopolysaccharides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000097:blood* / Q000150:complications
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester