Effects of phyllanthin and hypophyllanthin on vascular tension of isolated rat aorta

Abstract

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. The results indicated that both phyllanthin and hypophyllanthin (1-100 µM) 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. In endothelium-denuded rings, vasorelaxant inhibitors [atropine (1 µM), BaCl2 (10 µM), glybenclamide (10 µM), indomethacin (10 µM), L-NAME (100 µM), methylene blue (10 µM), propranolol (10 µM), 4-aminopyridine (100 µM) and TEA (10 µM)] did not inhibit the vasorelaxation responses induced by either phyllanthin or hypophyllanthin (100 µM). The data also demonstrated that the two lignans were able to induce aortic contraction which could be suppressed by either tyramine or prazosin. In addition, both compounds inhibited the PE- and KCl-mediated contraction of aortic muscle in concentration-dependent manner. Furthermore, these two compounds (100 µM) also significantly inhibited the Ca2+- induced contraction of aortic muscles that were depleted of Ca2+. However, only phyllanthin (100 µM), but not hypophyllanthin was able to inhibit the Ca2+- mediated contraction in high K+ - Ca2+- free condition. 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 effect of the test compounds were likely involved with the inhibition of Ca2+ influx as well as with the inhibition of PE-mediated Ca2+ release from sarcoplasmic reticulum.