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) 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.

Cellular Effects of Pyocyanin, a Secreted Virulence Factor of Pseudomonas aeruginosa

“…Studies have been undertaken assessing the impact of PCN on respiratory, urological, neurological, cardiovascular, and hepatic models, both in vitro and in vivo [27,28,29,30,31,33,48,50,51], with the majority of these studies undertaken in in vitro systems. These studies have highlighted the diverse range of effects that PCN has on the host, including pro-inflammatory [11,12,33] and immunomodulating properties [33].…”

“…Few studies have evaluated the effects of PCN on the vascular system to date, and those available are limited to in vitro studies [29,77,78]. However, P. aeruginosa is a rare cause of infective endocarditis and is seen primarily in injection drug users and patients undergoing cardiac procedures [3,4,5,6].…”

“…Vascular manifestations may also arise from P. aeruginosa sepsis, a life-threatening systemic infection that is becoming more prevalent in society [79]. PCN, at physiologically relevant concentrations, has been shown to inhibit vasorelaxation of porcine coronary arteries via both nitric oxide-dependent [29,77] and -independent mechanisms [29]. A recent study has shown that CF patients experience endothelial dysfunction [78] which may be further exacerbated through exposure to PCN.…”

“…Given the high incidence of chronic colonization with P. aeruginosa in cystic fibrosis (CF), the majority of research on PCN to date has primarily been focused on its effect on human airway. However, recently there have been a number of studies demonstrating the broader consequences of PCN exposure, especially in the urinary tract [27,28], the cardiovascular system [29], and the CNS [30,31]. In light of this, the focus of the review is to highlight the diverse cellular effects of PCN in vitro, in vivo, and in humans.…”

Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor‐associated anemia

“…Erythrocytes from newborns are highly sensitive to oxidative stress leading to rapid eryptosis and subsequent clearance of those erythrocytes following birth . Eryptosis is triggered by complement, hyperosmotic shock, energy depletion, oxidative stress, cellular K + loss, hyperthermia and a wide variety of xenobiotics including diverse cytostatic drugs (see below).…”