966 EPIGALLOCATECHIN GALLATE ENHANCES THE ENDOTHELIUM-INDEPENDENT VASORELAXATION OF THE ANTI-ATHEROSCLEROTIC CA2+ CHANNEL BLOCKING PEPTIDE TRP-HIS IN THORACIC AORTA FROM SPRAGUE-DAWLEY RATS

Abstract

Objectives: To enhance the benefit of drugs for cardiovascular diseases and reduce their side effects, combination drug therapy could be useful strategy, which can be applied to functional food components. Thus, the aim of this study was to demonstrate the enhancement of the vasorelaxation power of the anti-atherosclerotic L-type Ca2+ channel (VDCC) blocking peptide Trp-His by catechins. Methods: Vasorelaxation was recorded in contracted aorta rings from male 8 wk Sprague-Dawley rats. Results: We found that epigallocatechin gallate (EGCg, 300 μM) dramatically enhanced the magnitude of vasorelaxation of Trp-His by a factor of >6 (EC50 of Trp-His: EGCg(-), 2.80 ± 0.05 mM; EGCg (+), 0.45 ± 0.04 mM) in 1.0 μM phenylephrine-contracted rat aorta, while other catechins (epicatechin, epicatechin gallate and epigallocatechin) did not show any effect. Since the enhancing effect of EGCg was completely abolished in endothelium-removed aorta and high K+ (70 mM KCl)-contracted aorta, activation of endothelium-derived relaxing factors such as nitric oxide (NO) and membrane hyperpolarization in vascular endothelium induced by EGCg might be involved in the enhanced vasorelaxation. The enhancement of Trp-His-induced vasorelaxation by EGCg was significantly diminished by either NG-monomethyl-L-arginine acetate (nitric oxide synthase inhibitor) or 1-H-[1,2,4]oxadiazolo[4,3]quinoxalin-1-one (soluble guanylyl cyclase inhibitor), indicating the possible involvement of NO/cGMP pathway in mediating this effect. EGCg also enhanced the vasorelaxation of the VDCC blocker nifedipine. Conclusions: These results suggest that the Trp-His-induced vasorelaxation via the VDCC blocking is significantly potentiated by the activation of the NO/cGMP pathway by EGCg.