Effects of quercetin and rutin on vascular preparations - A comparison between mechanical and electrophysiological phenomena

Background Several studies have indicated that quercetin promotes relaxation of vascular smooth muscle both in vivo and in vitro. However, Saponara et al. [ (2002) Br J Pharmacol 135:1819-1827] have demonstrated that quercetin is an activator of vascular L-type Ca2+ channels. Aim of the study We investigated the mechanical and electrophysiological properties of quercetin and its rutoside, rutin, in an attempt to clarify how Ca2+ channel activation might be related to the myorelaxing activity. Methods Aorta ring preparations and single tail artery myocytes were employed for functional and patch-clamp experiments, respectively. Results Rutin was found to relax intact rat aorta rings, which had been precontracted with phenylephrine (pIC(50) = 5.65 +/- 0.31) but in contrast had no effect on depolarised (60 mM K+) preparations or on those from which the endothelium had been removed. Furthermore, rutin did not affect L-type Ca2+ current recorded in rat tail artery myocytes. The quercetin-induced relaxation of intact rings precontracted with phenylephrine exhibited two components characterised by 6.23 +/- 0.38 and 4.66 +/- 0.09 pIC(50), respectively. Removal of the endothelium abolished the first component, leaving the second unaltered. Moreover, quercetin was found to relax 60 mM K+ depolarised rings with a pIC(50) of 4.59 +/- 0.03. The application of quercetin in isolated smooth muscle cells brought about a marked increase of L-type Ca2+ current (pEC(50) = 5.09 +/- 0.05). Unlike quercetin, Bay K 8644 contracted aorta rings preincubated with 10, 20 or 30 mM K+. The myotonic effect of Bay K 8644 was observed both in the absence or presence of 30 muM quercetin. The application of Bay K 8644 (10-100 nM) caused a further significant increase in L-type Ca2+ current in rat tail artery myocytes stimulated with 30 muM quercetin. Conclusions Quercetin is a naturally occurring L-type Ca2+ channel agonist. This effect, however, is overwhelmed by quercetin-induced vasorelaxation taking place via pathways which are more relevant than L-type Ca2+ influx in the hierarchy of functional competencies.