Involvement of bradykinin and nitric oxide in the early hemodynamic effects of lipopolysaccharide in rats.
The involvement of bradykinin and nitric oxide (NO) in the early (within 1 h) hemodynamic effects of bacterial lipopolysaccharide (LPS) were investigated in anaesthetised rats. Infusion of rats with LPS (14 mg/kg/h) produced a transient hypotension (nadir at 20 min) and reduced pressor responses to noradrenaline (NA,.1-1 microgram/kg, intravenously (i.v.)). Pretreatment of rats with NG-nitro-L-arginine methylester (L-NAME, 1 mg/kg, i.v.) produced a hypertension which counteracted but did not abolish the hypotension induced by LPS, although it entirely prevented LPS-induced hyporeactivity to NA. In control rats, the bradykinin B2 receptors antagonist HOE 140 (10 nmol/kg, i.v.) produced a transient hypotension, but it did not modify the reactivity to NA. In rats pretreated with HOE 140, subsequently infused with LPS, the drop in blood pressure and its time course after the onset of LPS infusion were not different from those elicited by HOE 140 or LPS separately. In addition, HOE 140 partially prevented the onset of hyporesponsiveness to NA induced by LPS. These results support the view that both bradykinin and NO are involved in the early hyporesponsiveness to NA. They suggest that other mechanisms than NO release are involved in the early hypotensive effects of LPS.
Paya
D
D
Université Louis Pasteur de Strasbourg, Laboratoire de Pharmacologie Cellulaire et Moléculaire, CNRS URA 600, Illkirch, France.
Stoclet
J C
JC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D012772:Shock, Septic / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*
D065168:Bradykinin Receptor Antagonists; D008070:Lipopolysaccharides; D043782:Receptor, Bradykinin B2; D009569:Nitric Oxide; C065679:icatibant; D001120:Arginine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine