The Pseudomonas aeruginosa quorum-sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, inhibits porcine arterial smooth muscle contraction

The Pseudomonas aeruginosa quorum sensing molecule N-(3-oxododecanoyl)-L-ho moserine lactone (OdDHL) has been shown to suppress cytokine production in macrophages. We have examined the effect of OdDHL and related compounds on constrictor tone of porcine blood vessels. OdDHL (1-30 mu M) caused a conce ntration-dependent inhibition of U46619-induced contractions of the coronar y artery through a largely endothelium-independent mechanism, but was marke dly less effective in the pulmonary artery. Quantitively similar effects to those produced by OdDHL were observed with N-(3-oxododecanoyl)-L-homocyste ine thiolactone, a thiolactone derivative, while N-3-oxododecanamide, a lac tone-free acyl analogue, possessed 1/3rd the potency as a vasorelaxant. Nei ther N-butanoyl-L-homoserine lactone nor L-homoserine lactone (up to 30 mu M) were active. Our findings indicate that OdDHL inhibits vasoconstrictor t one of both pulmonary and coronary blood vessels from the pig. The vasorela xant action of OdDHL appears to be primarily determined by the N-acyl chain length, with a minor contribution by the homoserine lactone moiety.