Interleukin-1 contributes to the induction of nitric oxide synthase by endotoxin in vivo.
We investigated the role of interleukin-1 in the induction of a Ca(2+)-independent nitric oxide (NO) synthase by bacterial endotoxin in vivo. In anaesthetized rats, pretreatment with interleukin-1 receptor antagonist (interleukin-1ra; 16 mg kg-1 i.v., followed by an infusion of 2.4 mg kg-1 h-1) ameliorated the delayed hypotension and tachycardia in response to endotoxin (2 mg kg-1 i.v.). Endotoxaemia for 3 h induced a Ca(2+)-independent NO synthase activity in the lung and reduced the contractions to noradrenaline in the thoracic aorta ex vivo. Treatment with interleukin-1ra attenuated both the induction of NO synthase in the lung (by 46 +/- 5%) and the endotoxin-induced hyporeactivity to noradrenaline in the aorta. Thus, endogenous interleukin-1 contributes to the induction of NO synthase in response to endotoxin in vivo.
Szabó
C
C
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Wu
C C
CC
Gross
S S
SS
Thiemermann
C
C
Vane
J R
JR
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D004926:Escherichia coli; D006339:Heart Rate / Q000187:drug effects; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000201:enzymology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019001:Nitric Oxide Synthase; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology
D004731:Endotoxins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009638:Norepinephrine