Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis

J. Meyer, L. D. Traber, S. Nelson, C. W. Lentz, H. Nakazawa, D. N. Herndon, H. Noda, D. L. Traber

Research output: Contribution to journalArticlepeer-review

128 Scopus citations


Septic shock is characterized by an increase in cardiac output and a fall in systemic vascular resistance index and mean arterial pressure. Endotoxin alters the smooth muscle function of blood vessels, probably by means of an increased production of the potent vasodilator nitric oxide (NO). The present study was accomplished to determine how the inhibition of NO synthesis influences cardiovascular performance in an ovine model of hyperdynamic endotoxemia. Endotoxemia was induced in five range ewes (41 ± 2 kg) by continuous infusion of Escherichia coli endotoxin (LPS, 10 ng · kg-1 · min-1) over the entire study period. After 24 h of LPS infusion, cardiac output increased from 5.2 ± 0.3 to 7.9 ± 0.6 (SE) 1/min (P < 0.05) and mean arterial pressure and systemic vascular resistance index fell from 92 ± 5 to 79 ± 6 mmHg (P = 0.08) and from 1,473 ± 173 to 824 ± 108 dyn · s · cm- 5 · m2 (P < 0.05), respectively. The pulmonary shunt fraction increased from 0.23 ± 0.03 to 0.32 ± 0.03 (P < 0.05). The intravenous administration of the NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (25 mg/kg) 24 h after the start of the LPS infusion changed these values to approximately baseline levels over the subsequent 4 h. Although N(ω)-nitro- L-arginine methyl ester increased pulmonary arterial pressure and pulmonary vascular resistance (P < 0.05), right and left ventricular stroke volume index showed no significant changes. It is concluded that NO has a major function in cardiovascular performance in endotoxemia. Inhibition of NO synthesis may be a useful adjunct in the treatment of hyperdynamic sepsis.

Original languageEnglish (US)
Pages (from-to)324-328
Number of pages5
JournalJournal of Applied Physiology
Issue number1
StatePublished - 1992


  • L-arginine
  • N(ω)- nitro-L-arginine methyl ester
  • cardiac output
  • endothelium-derived relaxing factor
  • sepsis
  • septic shock
  • systemic vascular resistance

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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