Pyocyanin inhibits both nitric oxide-dependent and -independent relaxation in porcine coronary arteries.
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) F2α or potassium chloride and endothelium-dependent relaxations were induced by various agents in the presence of PCN. Pyocyanin (0.1-10 μmol/L) evoked small-amplitude, dose-dependent contractions in resting porcine coronary arteries. In addition, PCN amplified the contractile response to PGF2α , but did not alter responses to carbachol. Pyocyanin (0.1-10 μmol/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 (β-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.
School of Health Science, Bond University, Gold Coast, Qld, Australia.
Allison
A
Hempenstall
Gary D
GD
Grant
Shailendra
S
Anoopkumar-Dukie
Peter J
PJ
Johnson
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D004048:Diethylamines / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D011710:Pyocyanine / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D004048:Diethylamines; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D011710:Pyocyanine; C034281:diethylamine; D015237:Dinoprost; C044258:8-chloro-cyclic adenosine monophosphate; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol
Pseudomonas aeruginosa; coronary artery; nitric oxide; pyocyanin