Endothelium-independent effects of phyllanthin and hypophyllanthin on vascular tension.

The purpose of this study was to investigate the modulating effects of phyllanthin and hypophyllanthin on vascular tension, using in the in vitro model of isolated rat aorta. Our results indicated that both phyllanthin and hypophyllanthin significantly relaxed the sustained contraction induced by phenylephrine (PE) in a concentration-dependent manner. In addition, endothelial removal had no significant influence on the vasorelaxation responses of the aortic rings toward these two compounds. Furthermore, both compounds inhibited the contraction of aortic muscle provoked by either PE (1 μM) or KCl (40 mM) as well as the spontaneous contraction of the Ca²⁺-depleted muscle. In high K⁺-Ca²⁺ free solution, phyllanthin (100 μM), but not hypophyllanthin, significantly inhibited the contractile responses upon cumulative addition of CaCl₂. Both compounds (100 μM) significantly inhibited PE-induced contraction in Ca²⁺-free condition, but could not affect caffeine-induced contraction. Taken together, phyllanthin and hypophyllanthin could modulate the vascular tension via the endothelium-independent mechanisms. The modulating effects of both compounds were possibly involved with the blockade of Ca²⁺ entry into vascular smooth muscle cells and inhibition of PE-mediated Ca²⁺ release from sarcoplasmic reticulum.