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Acta Physiologica 2007; Volume 190, Supplement 656
The Scandinavian Physiological Society's Annual Meeting
8/10/2007-8/12/2007
Oslo, Norway
ROLE OF CYCLOOXYGENASE-2 FOR LIPOPOLYSACCHARIDE-MEDIATED VASORELAXATION
Abstract number: P08
Staehr1 M, Madsen1 K, Hansen1 PBL, Skott1 O, Jensen1 BL
1Institute of Medical Biology - Physiology and Pharmacology, J.B. Winslws Vej 21, DK-5000 Odense C, Denmark
In a model of endotoxemic shock, a COX-2 inhibitor improved the cardiovascular status of lipopolysaccharide (LPS) treated rats. We hypothesized that LPS-induced suppression of vasoreactivity is caused by stimulation of COX-2 expression and downstream activation of eNOS by PGE2 in the vessels. To address this, rings from mouse aorta were incubated with LPS 10, 50 or 100 mg/mL (055:B5, Sigma) for 18h at 37°C in cell culture medium and then mounted in an isometric myograph. The contractile response was tested with cumulative doses of phenylephrine (PE) (2*107 M 3 *106 M), followed by Acetylcholine (106 M) to test endothelial function. After wash and equilibration, the rings were contracted for 1 h with PE (2* 107 M). At 50 mg/mL LPS, the rings exhibited a stable reduction in contractility (15.7%±0.3 of control, n=6) whereas at 10 mg/mL and 100 mg/mL there were no significant change 72.6%±1.99, (n=7) and 74.4%±6.85, (n=4) respectively. Rings were then incubated with LPS (50 mg/mL) and L-NAME (104 M, Sigma), a NOS inhibitor. L-NAME abolished the effect of LPS on vasoreactivity and no significant difference in response to PE was observed (n=6). Aortic rings prepared from COX-2 knock out mice and wild-type littermates displayed no difference in reactivity to PE (2*107 M) compared to control mice. Rings from COX-2-/- and wildtype mice were incubated with LPS (50 mg/mL, n=5) but the absence of functional COX-2 did not attenuate the suppression of contractility in response to PE. We conclude that LPS significantly suppresses vasoreactivity in an isolated vessel preparation through increased NO synthesis independent of COX-2.
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Acta Physiologica 2007; Volume 190, Supplement 656 :P08