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Bactericidal/permeability‐increasing protein inhibits endotoxin‐induced vascular nitric oxide synthesis
Author(s) -
Ciornei C. D.,
Egesten A.,
Engström M.,
Törnebrandt K.,
Bodelsson M.
Publication year - 2002
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1034/j.1399-6576.2002.460909.x
Subject(s) - lipopolysaccharide , nitric oxide synthase , nitric oxide , phenylephrine , vascular smooth muscle , medicine , pharmacology , contractility , septic shock , western blot , biochemistry , sepsis , chemistry , blood pressure , smooth muscle , gene
Background: Endotoxin (lipopolysaccharide, LPS) up‐regulates inducible nitric oxide synthase (iNOS) in blood vessels during septic shock. This promotes the production of nitric oxide (NO), leading to dilation of the vessels. The aim of the study was to investigate the effects of the LPS‐binding endogenous antibiotic bactericidal/permeability‐increasing protein (BPI) on the action of LPS on the blood vessels wall and to identify possible influence on underlying NO‐related mechanisms. Methods: Isolated segments of rat thoracic aorta and cultured primary smooth muscle cells were incubated for 5–48 h in the presence of the following combinations of compounds: (a) LPS; (b) interleukin‐1β (IL‐1β); (c) BPI; (d) BPI + LPS; (e) BPI + IL‐1β or (f) neither BPI, LPS nor IL‐1β (control). After incubation of intact segments, we measured smooth muscle contraction in response to phenylephrine and accumulation of the NO end products nitrate and nitrite in surrounding medium. Western blot was used to assess the levels of inducible nitric oxide synthase (iNOS) in cultured cells. Results: Both LPS and IL‐1β decreased contractility and increased NO production, as well as iNOS. Co‐incubation with BPI attenuated all the effects of LPS but only the effects of prolonged exposure to IL‐1β in cultured cells. Conclusion: We conclude that BPI attenuates the LPS‐induced changes in vascular reactivity by inhibiting the expression of iNOS resulting in decreased NO formation and restored responsiveness to vasoconstrictors. The data suggest that BPI can prevent circulatory disturbances during Gram‐negative sepsis.