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 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.