Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta.
In order to determine whether endotoxemia induced generalized defects in vascular contraction and endothelium-dependent relaxation, we studied the effect of in vivo endotoxin administration in Sprague-Dawley rats and New Zealand White rabbits on endothelial and arterial smooth-muscle responses of isolated thoracic aorta in vitro. Endotoxin treatment significantly decreased contractile responses to phenylephrine (PE), angiotensin II (AII), serotonin (5-HT), and potassium chloride. This effect was not altered by indomethacin or endothelial denudation. Treatment of vessels with NG-nitro-L-arginine (NNLA), an inhibitor of arginine-dependent nitric oxide biosynthesis, or with methylene blue, an inhibitor of soluble guanylate cyclase, resulted in significant improvement of the contractile defect in endotoxin-treated vessels. The restorative effect of NNLA on contractile responses in endotoxin-treated aortic rings was similar in the presence or absence of an intact endothelium. Endothelium-dependent relaxation in response to acetylcholine, substance P, or the calcium ionophore A23187 was markedly impaired in vessels from endotoxin-treated rabbits, while endothelium-independent relaxation in response to nitroprusside was similar in both groups. These results suggest that endotoxemia both induces basal, nonendothelial nitric oxide synthesis and impairs the agonist-stimulated release of endothelium-derived relaxing factor (EDRF). These findings may have mechanistic importance in the hemodynamic derangements of endotoxemia.
Umans
J G
JG
Department of Medicine, University of Chicago, Illinois 60637.
Wylam
M E
ME
Samsel
R W
RW
Edwards
J
J
Schumacker
P T
PT
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004731:Endotoxins; D008070:Lipopolysaccharides; D000804:Angiotensin II; D010656:Phenylephrine; D019335:Nitroarginine; D012701:Serotonin; D011189:Potassium Chloride; C044101:endotoxin, Escherichia coli; D001120:Arginine; D008751:Methylene Blue; D007213:Indomethacin