Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta

J. G. Umans, Mark Wylam, R. W. Samsel, J. Edwards, P. T. Schumacker

Research output: Contribution to journalArticle

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Abstract

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 N(G)-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.

Original languageEnglish (US)
Pages (from-to)1638-1645
Number of pages8
JournalAmerican Review of Respiratory Disease
Volume148
Issue number6 I
StatePublished - Dec 1 1993
Externally publishedYes

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Endotoxins
Smooth Muscle
Aorta
Endotoxemia
Rabbits
Endothelium
Arginine
Serotonin
Nitric Oxide
Endothelium-Dependent Relaxing Factors
Potassium Chloride
Calcium Ionophores
Methylene Blue
Calcimycin
Nitroprusside
Phenylephrine
Substance P
Thoracic Aorta
Vasodilation
Indomethacin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta. / Umans, J. G.; Wylam, Mark; Samsel, R. W.; Edwards, J.; Schumacker, P. T.

In: American Review of Respiratory Disease, Vol. 148, No. 6 I, 01.12.1993, p. 1638-1645.

Research output: Contribution to journalArticle

Umans, JG, Wylam, M, Samsel, RW, Edwards, J & Schumacker, PT 1993, 'Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta', American Review of Respiratory Disease, vol. 148, no. 6 I, pp. 1638-1645.
Umans, J. G. ; Wylam, Mark ; Samsel, R. W. ; Edwards, J. ; Schumacker, P. T. / Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta. In: American Review of Respiratory Disease. 1993 ; Vol. 148, No. 6 I. pp. 1638-1645.
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