Quercetin prevents LPS-induced hyporesponsiveness of vascular responses of the porcine isolated coronary artery

Salmin Al-Shalmani1, Sunita Suri1, Moira Taylor1, P Kroon2, D Hughes2, S Triboli2, Vincent Wilson1

1School of Biomedical Sciences, University of Nottingham, Nottingham, UK, 2Institute of Food Research, Norwich, UK

The flavonoid quercetin has been reported to inhibit lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines and nitric oxide in macrophages (Kim et al., 2005). This effect is consistent with the reported benefits of dietary flavonoids on cardiovascular health (Boots et al., 2008). LPS is known to impair vasoconstrictor responses in isolated blood vessels, in part by the induction of nitric oxide synthase (Qi et al., 2007), yet surprisingly the effect of quercetin has not been examined. We have investigated the effect of quercetin on LPS-induced hyporesponsiveness in the porcine coronary artery.

Segments of the porcine isolated coronary artery were incubated overnight at 37°C in Krebs-Henseleit solution containing 10% foetal bovine serum and antibiotics with or without either 1μg/ml LPS (E.Coli. O111:B4) or 1μg/ml LPS and 10μM quercetin (Qi et al., 2007). The following day segments were prepared for isometric tension recording and then exposed to cumulative concentrations of either KCl or the thromboxane-mimetic U46619. Responses have been expressed as grams weight and the potency as the negative logarithm of the concentration causing 50% of the maximum response (-log EC50). Data are shown as mean ± sem and differences between LPS and LPS& quercetin considered statistically significant by paired Student’s t-test (two-tailed, p<0.05)*.

Following exposure to 1μg/ml LPS the maximum response to KCl and U46619 was reduced by 38.8±3.5% (n=13) and 20.3±6.0% (n=13), respectively, with no change in potency to either constrictor. In a separate experiment prior exposure to 10μM quercetin reduced the inhibitory effect of 1μg/ml LPS on KCl- and U46619 responses, but only the former reached statistical significance (Table 1). Endothelium-dependent relaxations to 10nM substance P (25.8±5.7%, n=13) were significantly reduced after 1μg/ml LPS (9.4±1.9%, n=13), but this effect was prevented by 10μM quercetin (23.3±3.8%, n=13).

This is the first demonstration that LPS-induced hyporesponsiveness of constrictor and endothelium-dependent relaxations is prevented by the major dietary flavonoid quercetin. Further studies are warranted to establish whether this effect involves alteration in the expression of nitric oxide synthase.

Boots AW et al., (2008). Eur. J. Pharmacol. 585, 325-337

Kim L et al., (2005). Biochem. Pharmacol. 69, 1577-1583

Qi, W. et al., (2007). Br. J. Anaesthesia. 98, 323-330