Effects of in vivo lipopolysaccharide infusion on vasoconstrictor function of rat isolated mesentery, kidney, and aorta.
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 microM, 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.
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Clifton Boulevard, Nottingham, NG7 2UH, United Kingdom.
Matthew R
MR
Farmer
Richard E
RE
Roberts
Sheila M
SM
Gardiner
Vera
V
Ralevic
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000503:physiopathology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D008643:Mesentery / Q000187:drug effects / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D008729:Methoxamine; D002118:Calcium