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This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/H1177    most recent 00997.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Mansart, A. Articles by Atkinson, J. Search for Related Content PubMed PubMed Citation Articles by Mansart, A. Articles by Atkinson, J.

Effects of dexamethasone and L-canavanine on the intracellular calcium-contraction relation of the rat tail artery during septic shock

¹Pharmacology Laboratory, Pharmacy Faculty, Nancy University, and ²Intensive Care Unit, University Central Hospital, Nancy, France

Submitted 19 September 2005 ; accepted in final form 27 March 2006

The intracellular mechanism by which sepsis lowers vascular reactivity and the subsequent reversal by dexamethasone or nitric oxide synthase (NOS) inhibitors remain unclear. We measured the sensitivity of contraction of the rat tail artery to intracellular Ca²⁺ in a model of polymicrobial septic shock. At 22 h after cecal ligation and puncture (CLP), rats were treated with an anti-inflammatory glucocorticoid (dexamethasone, 1 mg/kg ip), an inducible NOS inhibitor (L-canavanine, 100 mg/kg ip), or saline. At 24 h after CLP, endothelium-denuded, perfused segments of tail artery were loaded with the intracellular Ca²⁺-sensitive dye fura 2 in vitro. Intracellular Ca²⁺ concentration and perfusion pressure were measured simultaneously. The rightward shift of the perfusion pressure-intracellular Ca²⁺ mobilization curve after norepinephrine stimulation subsequent to CLP indicates decreased intracellular Ca²⁺ sensitivity of contraction. The relation was restored by dexamethasone (which also restored in vivo blood pressure and flow), but not by L-canavanine (which restored perfusion pressure by further mobilization of intracellular Ca²⁺). We conclude that CLP lowers vasomotion by lowering intracellular Ca²⁺ sensitivity, which can be restored with glucocorticoid treatment. The involvement of inducible NOS does not solely account for the sepsis-induced reduction in Ca²⁺ sensitivity of contraction.

glucocorticoid; nitric oxide; sepsis