ABSTRACT
BACKGROUND AND PURPOSE: The cardiovascular benefits of red wine consumption are often attributed to the antioxidant effects of its polyphenolic constituents, including quercetin, catechin and resveratrol. Inhibition of cardiac voltage-gated sodium channels (VGSCs) is antiarrhythmic and cardioprotective. As polyphenols may also modulate ion channels, and possess structural similarities to several antiarrhythmic VGSC inhibitors, we hypothesised that VGSC inhibition may contribute to cardioprotection by these polyphenols. EXPERIMENTAL APPROACH: The whole-cell voltage-clamp technique was used to record peak and late VGSC currents (INa) from recombinant human heart NaV1.5 channels expressed in tsA201 cells. Right ventricular myocytes from rat heart were isolated and single myocytes were field-stimulated. Either calcium transients or contractility were measured using the calcium-sensitive dye Calcium-Green 1AM or video edge detection, respectively. KEY RESULTS: The red grape polyphenols quercetin, catechin and resveratrol blocked peak INa with IC50s of 19.4 microM, 76.8 microM and 77.3 microM, respectively. In contrast to lidocaine, resveratrol did not exhibit any frequency-dependence of peak INa block. Late INa induced by the VGSC long QT mutant R1623Q was reduced by resveratrol and quercetin. Resveratrol and quercetin also blocked late INa induced by the toxin, ATX II, with IC50s of 26.1 microM and 24.9 microM, respectively. In field-stimulated myocytes, ATXII-induced increases in diastolic calcium were prevented and reversed by resveratrol. ATXII-induced contractile dysfunction was delayed and reduced by resveratrol. CONCLUSIONS AND IMPLICATIONS: Our results indicate that several red grape polyphenols inhibit cardiac VGSCs and that this effect may contribute to the documented cardioprotective efficacy of red grape products.
Subject(s)
Flavonoids/pharmacology , Heart/drug effects , Ion Channel Gating/drug effects , Phenols/pharmacology , Sodium Channels/drug effects , Vitis/chemistry , Animals , Base Sequence , Calcium/metabolism , Cell Line , DNA Primers , Mutagenesis, Site-Directed , Polyphenols , RatsABSTRACT
The differential criterion-related validity of the MMPI and MMPI-2 and their stability over a 4-month period of time were examined in a university population by correlating the clinical scales with their counterpart SCL-90-R factors. Fair to moderate correlations were found on all eight paired MMPI scales and SCL-90-R factors, while only two of eight MMPI-2/SCL-90-R pairings were found to be correlated significantly. Further analyses, however, found no significant differences between these MMPI/SCL-90-R and MMPI-2/SCL-90-R correlations. Adequate stability was found between MMPI-2 and SCL-90-R pairs over 4 months, except for the MMPI-2 D scale with the SCL-90-R Depression factor. Several issues related to the equivalency between the MMPI and the MMPI-2 were discussed.
