Pyocyanin inhibits both nitric oxide-dependent and -independent relaxation in porcine coronary arteries

Abstract

The effects of the Pseudomonas aeruginosa virulence factor pyocyanin (PCN) on the contractile function of porcine coronary arteries was investigated in vitro. Artery rings (5 mm) were suspended in organ baths containing Krebs’ solution for the measurement of isometric tension. The effect of PCN on resting and precontracted coronary arteries was initially investigated with various agents. Arteries were precontracted with prostaglandin (PG) F2a or potassium chloride and endothelium- dependent relaxations were induced by various agents in the presence of PCN. Pyocyanin (0.1–10 lmol/L) evoked small-amplitude, dose-dependent contractions in resting porcine coronary arteries. In addition, PCN amplified the contractile response to PGF2a, but did not alter responses to carbachol. Pyocyanin (0.1–10 lmol/L) significantly inhibited endothelium-dependent relaxations evoked by neurokinin A. Pyocyanin also inhibited relaxations evoked by diethylamine nitric oxide (a nitric oxide donor), forskolin (an adenylate cyclase activator), dibuytyryl-cAMP (a cAMP analogue), 8- bromo-cGMP (a cGMP analogue) and P1075 (a KATP channel activator), but not isoprenaline (b-adrenoceceptor agonist). These results indicate that physiological concentrations of PCN interfere with multiple intracellular processes involved in vascular smooth muscle relaxation, in particular pathways downstream of nitric oxide release. Thus, PCN may alter normal vascular function in patients infected with P. aeruginosa. Key words: coronary artery, nitric oxide, Pseudomonas aeruginosa, pyocyanin.