Effect of bacterial lipopolysaccharide on function of rat small femoral arteries.
The effects of endotoxin on endothelial and smooth muscle function were investigated in small femoral arteries removed from rats 4 h after intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 20 mg/kg) or solvent. In the absence of L-arginine in the organ bath, the sensitivity of the arteries to norepinephrine (NE) was decreased only slightly, and the relaxing effects of neither 3-morpholinosydonimine-N-ethyl-carbamide (SIN-1), a nitric oxide (NO) donor, nor acetylcholine (ACh) were modified by LPS treatment despite morphological damage to the endothelium seen with scanning electron microscopy. However, L-arginine (30 microM to 1 mM), which had no effect on control vessels, caused a rapid and stereospecific relaxation of arteries from LPS-treated rats that was abolished by both NG-nitro-L-arginine methyl ester (1 mM), a NO synthase inhibitor, and methylene blue, an inhibitor of the activation of guanylyl cyclase by NO. The relaxing effect of L-arginine was observed in the absence of endothelium, although it was significantly greater in its presence. In addition, a 30-min exposure to extracellular L-arginine (100 microM) moderately but significantly decreased the sensitivity to ACh and SIN-1 of vessels from LPS-treated but not from control rats. These results indicate that LPS treatment induced a NO synthase activity in smooth muscle cells of rat small femoral arteries and that the resulting relaxation was dependent on extracellular L-arginine in these resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Schneider
F
F
Laboratoire de Pharmacologie Cellulaire et Moléculaire, Université Louis Pasteur de Strasbourg, Illkirch, France.
Bucher
B
B
Schott
C
C
Andre
A
A
Julou-Schaeffer
G
G
Stoclet
J C
JC
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004926:Escherichia coli; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects
D008070:Lipopolysaccharides; D001120:Arginine