Quercetin and its principal metabolites, but not myricetin, oppose lipopolysaccharide-induced hyporesponsiveness of the porcine isolated coronary artery

BACKGROUND AND PURPOSE Quercetin is anti-inflammatory in macrophages by inhibiting lipopolysaccharide (LPS)-mediated increases in cytokine and nitric oxide production but there is little information regarding the corresponding effect on the vasculature. We have examined the effect of quercetin, and its principal human metabolites, on inflammatory changes in the porcine isolated coronary artery. EXPERIMENTAL APPROACH Porcine coronary artery segments were incubated overnight at 37 degrees C in modified Krebs-Henseleit solution with or without 1 mu g center dot mL-1 LPS. Some segments were also co-incubated with quercetin-related flavonoids or Bay 11-7082, an inhibitor of NF kappa B. Changes in isometric tension of segments to vasoconstrictor and vasodilator agents were recorded. Nitrite content of the incubation solution was estimated using the Griess reaction, while inducible nitric oxide synthase was identified immunohistochemically. KEY RESULTS Lipopolysaccharide reduced, by 35-50%, maximal contractions to KCl and U46619, thromboxane A(2) receptor agonist, and impaired endothelium-dependent relaxations to substance P. Nitrite content of the incubation medium increased 3- to 10-fold following exposure to LPS and inducible nitric oxide synthase was detected in the adventitia. Quercetin (0.1-10 mu M) opposed LPS-induced changes in vascular responses, nitrite production and expression of inducible nitric oxide synthase. Similarly, 10 mu M Bay 11-7082, 10 mu M quercetin 3'-sulphate and 10 mu M quercetin 3-glucuronide prevented LPS-induced changes, while myricetin (10 mu M) was inactive. Myricetin (10 mu M) prevented quercetin-induced modulation of LPS-mediated nitrite production. CONCLUSION AND IMPLICATIONS Quercetin, quercetin 3'-suphate and quercetin 3-glucuronide, exerted anti-inflammatory effects on the vasculature, possibly through a mechanism involving inhibition of NF kappa B. Myricetin-induced antagonism of the effect of anti-inflammatory action of quercetin merits further investigation.