Jg. Umans et al., EFFECTS OF ENDOTOXIN IN-VIVO ON ENDOTHELIAL AND SMOOTH-MUSCLE FUNCTION IN RABBIT AND RAT AORTA, The American review of respiratory disease, 148(6), 1993, pp. 1638-1645
In order to determine whether endotoxemia induced generalized defects
in vascular contraction and endothelium-dependent relaxation, we studi
ed the effect of in vivo endotoxin administration in Sprague-Dawley ra
ts and New Zealand White rabbits on endothelial and arterial smooth-mu
scle responses of isolated thoracic aorta in vitro. Endotoxin treatmen
t significantly decreased contractile responses to phenylephrine (PE),
angiotensin II (All), serotonin (5-HT), and potassium chloride. This
effect was not altered by indomethacin or endothelial denudation. Trea
tment of vessels with N-G-nitro-L-arginine (NNLA), an inhibitor of arg
inine-dependent nitric oxide biosynthesis, or with methylene blue, an
inhibitor of soluble guanylate cyclase, resulted in significant improv
ement of the contractile defect in endotoxin treated vessels. The rest
orative effect of NNLA on contractile responses in endotoxin-treated a
ortic rings was similar in the presence or absence of an intact endoth
elium. 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. Th
ese results suggest that endotoxemia both induces basal, nonendothelia
l nitric oxide synthesis and impairs the agonist-stimulated release of
endothelium-derived relaxing factor (EDRF). These findings may have m
echanistic importance in the hemodynamic derangements of endotoxemia.