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, David Herndon, H. Noda, D. L. Traber

Research output: Contribution to journalArticle

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Abstract

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
Volume73
Issue number1
StatePublished - 1992

Fingerprint

Endotoxins
Endotoxemia
Nitric Oxide
Vascular Resistance
Arterial Pressure
Cardiac Output
Lung
Septic Shock
Vasodilator Agents
Nitric Oxide Synthase
Intravenous Administration
Stroke Volume
Smooth Muscle
Blood Vessels
Sheep
Sepsis
arginine methyl ester
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Meyer, J., Traber, L. D., Nelson, S., Lentz, C. W., Nakazawa, H., Herndon, D., ... Traber, D. L. (1992). Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. Journal of Applied Physiology, 73(1), 324-328.

Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. / Meyer, J.; Traber, L. D.; Nelson, S.; Lentz, C. W.; Nakazawa, H.; Herndon, David; Noda, H.; Traber, D. L.

In: Journal of Applied Physiology, Vol. 73, No. 1, 1992, p. 324-328.

Research output: Contribution to journalArticle

Meyer, J, Traber, LD, Nelson, S, Lentz, CW, Nakazawa, H, Herndon, D, Noda, H & Traber, DL 1992, 'Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis', Journal of Applied Physiology, vol. 73, no. 1, pp. 324-328.
Meyer J, Traber LD, Nelson S, Lentz CW, Nakazawa H, Herndon D et al. Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. Journal of Applied Physiology. 1992;73(1):324-328.
Meyer, J. ; Traber, L. D. ; Nelson, S. ; Lentz, C. W. ; Nakazawa, H. ; Herndon, David ; Noda, H. ; Traber, D. L. / Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. In: Journal of Applied Physiology. 1992 ; Vol. 73, No. 1. pp. 324-328.
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AB - 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.

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