| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of Physiology, Anatomy and Cell Biology, and Pharmacology, New York Medical College, Valhalla, New York 10595
The relationship between plasma nitrite,
nitrate, and nitric oxide (NOx), cytokines, and cardiac and vascular
dysfunction after lipopolysaccharide (LPS) was studied in chronically
instrumented anesthetized dogs. LPS was administered (1 mg/kg iv), and
hemodynamics were recorded at baseline, every 15 min for 1 h, and every
hour for an additional 14 h. Dramatic reductions in mean arterial
pressure (
48 ± 6%), cardiac output (40 ± 8%),
stroke volume (42 ± 9%), and first derivative of left
ventricular pressure (LV dP/dt,
38 ± 7%) were seen within 1 h after injection of endotoxin.
Cardiac output was not different from control by 9 h, whereas mean
arterial pressure (19 ± 7%), stroke volume (32 ± 8%), and LV dP/dt (21 ± 10%) remained significantly depressed from control. Total peripheral resistance was not significantly different from control. Therefore, the
hypotension appears to be due to a reduction in cardiac function and
not to vasodilation. Levels of plasma NOx were not different from
control until 4 h after LPS reached levels 597 ± 126% higher than
control at 15 h. In vitro production of nitrite by coronary microvessels was also elevated, supporting our in vivo findings. In
contrast, production of tumor necrosis factor-
and interleukin-6 occurred shortly after endotoxin injection, reaching peak levels at 45 and 150 min, respectively. Our data suggest that inducible nitric oxide
synthase induction occurred after LPS injection. It is unlikely that
nitric oxide contributed significantly to the hypotension and cardiac
dysfunction early in our study, whereas cardiodepressive cytokines,
particularly tumor necrosis factor-, may be important. In contrast,
the hemodynamic effects seen late after injection of endotoxin may be
the result of an overproduction of nitric oxide, since there was a
sixfold increase in plasma NOx levels at this time and a marked
production of nitric oxide in isolated coronary microvessels in vitro.
plasma nitrate/nitrite; cytokines; tumor necrosis factor-; interleukin-6; stroke volume; cardiac output; coronary microvessels; N-nitro-L-arginine
methyl ester; aminoguanidine; S-methylisothiourea
This article has been cited by other articles:
|
|
 |
|
  E. K. Walsh, H. Huang, Z. Wang, J. Williams, R. de Crom, R. van Haperen, C. I. Thompson, D. J. Lefer, and T. H. Hintze Control of myocardial oxygen consumption in transgenic mice overexpressing vascular eNOS Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2115 - H2121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Lee, R. Leite, C. Fleming, J. S. Pollock, R. C. Webb, and M. W. Brands Hypertensive Response to Acute Stress Is Attenuated in Interleukin-6 Knockout Mice Hypertension, September 1, 2004; 44(3): 259 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Orshal and R. A. Khalil Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1013 - R1023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Pastor, A. Hadengue, and A. K. Nussler Minor involvement of nitric oxide during chronic endotoxemia in anesthetized pigs Am J Physiol Gastrointest Liver Physiol, March 1, 2000; 278(3): G416 - G424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Recchia, P. I. McConnell, R. D. Bernstein, T. R. Vogel, X. Xu, and T. H. Hintze Reduced Nitric Oxide Production and Altered Myocardial Metabolism During the Decompensation of Pacing-Induced Heart Failure in the Conscious Dog Circ. Res., November 16, 1998; 83(10): 969 - 979. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
