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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on May 2, 2003; DOI: 10.1124/jpet.103.051805


0022-3565/03/3062-538-545$20.00
JPET 306:538-545, 2003
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CARDIOVASCULAR

Effects of in Vivo Lipopolysaccharide Infusion on Vasoconstrictor Function of Rat Isolated Mesentery, Kidney, and Aorta

Matthew R. Farmer, Richard E. Roberts, Sheila M. Gardiner, and Vera Ralevic1

School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom

Continuous infusion of lipopolysaccharide (LPS) into conscious rats elicits regionally selective cardiovascular disturbances. The aim of the present study was to assess contractile function in different vascular preparations (renal, mesenteric, and thoracic aorta) taken from rats infused with LPS for 2 or 24 h. Sustained responses to continuous infusion of methoxamine but not to KCl were reduced in the aorta (at 2 and 24 h LPS) and mesentery (at 24 h LPS) but not in the renal vascular bed. In contrast, transient responses to bolus doses of methoxamine were unchanged in the mesentery. In Ca2+-imaging experiments with fura-2, challenge with a single concentration of methoxamine (10 µM, which showed an impaired contractile response at 24 h LPS) induced a rise in intracellular Ca2+ in the mesenteric artery that was not different from the control. Furthermore, in the aorta, the contractile response to caffeine was attenuated only in the 2 h LPS group. These results show that there is regional heterogeneity in in vitro vascular responsiveness in preparations taken from LPS-infused rats. Thus, in mesenteric beds and aortae, but not renal beds, there is hypocontractility to methoxamine that is not due to a generalized inability of the smooth muscle to contract, which is evident with sustained but not transient application of agonist (mesentery) and which, in late endotoxemia (24 h LPS), does not appear to involve abnormalities in Ca2+ mobilization or entry.


Received March 18, 2003; accepted April 22, 2003.

Address correspondence to: Dr. Vera Ralevic, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Clifton Boulevard, Nottingham, NG7 2UH, United Kingdom. E-mail: vera.ralevic{at}nottingham.ac.uk




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