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 (pIC50 = 5.65±0.3 1) 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 pIC50, 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 pIC50 of 4.59±0.03. The application of quercetin in isolated smooth muscle cells brought about a marked increase of L-type Ca2+ current (pEC50= 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 μM 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 μM 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.