Role of adventitial nitric oxide in vascular hyporeactivity induced by lipopolysaccharide in rat aorta.
This study was designed to elucidate the role of the adventitia in NO-mediated vascular effects of lipopolysaccharide (LPS). After incubation of rat aorta with LPS, the adventitia generated 3.5 times more nitrite plus nitrate than a corresponding segment of media. Control media covered by adventitia from LPS-treated aortic rings exhibited a 4 fold elevated level of cyclic GMP. Medial layers from LPS-treated aortic rings (like LPS-treated adventitia-intact rings) exhibited a decrease in sensitivity to noradrenaline (NA) that was reversed by 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (1 microM) or N omega-nitro-L-arginine methylester (0.3 mM). However, in contrast to LPS-treated adventitia-intact rings, medial layers showed no reduction in maximal contraction to NA and virtually no relaxation to L-arginine. These data indicate that in blood vessels exposed to LPS, the adventitia is a more powerful source of NO than the media. The adventitia-derived NO can reach soluble guanylyl cyclase in the medial layer and contribute greatly to vascular hyporeactivity and L-arginine-induced relaxation observed in blood vessels exposed to LPS.
Laboratoire de Pharmacologie et de Physiologie Cellulaires, Université Louis Pasteur de Strasbourg, CNRS ERS 653, Illkirch, France.
A L
AL
Kleschyov
B
B
Muller
C
C
Schott
J C
JC
Stoclet
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide