Effects of Ginkgo biloba extracts with mirodenafil on the relaxation of corpus cavernosal smooth muscle and the potassium channel activity of corporal smooth muscle cells

Abstract

In this study, we investigated the effects of a combination of Ginkgo biloba extracts (GBE) and phosphodiesterase type 5 (PDE-5) inhibitors on the muscular tone of the corpus cavernosum and potassium channel activity of corporal smooth muscle cells. Strips of corpus cavernosum from male New Zealand white rabbits were mounted in organ baths for isometric tension studies. After contraction with 1×10 -5 mol l -1 norepinephrine, GBE (0.01-1mg ml -1) and mirodenafil (0.01-100nmol l -1) were added together into the organ bath. In electrophysiological studies, whole-cell currents were recorded by the conventional patch-clamp technique in cultured smooth muscle cells of the human corpus cavernosum. The corpus cavernosum was relaxed in response to GBE in a dose-dependent manner (from 0.64%±8.35% at 0.01mg ml -1 to 52.28%±11.42% at 1mg ml -1). After pre-treatment with 0.03mg ml -1 of GBE, the relaxant effects of mirodenafil were increased at all concentrations. After tetraethylammonium (TEA) (1mmol l -1) administration, the increased effects were inhibited (P<0.01). Extracellular administration of GBE increased the whole-cell K + outward currents in a dose-dependent fashion. The increase of the outward current was inhibited by 1mmol l -1 TEA. These results suggest that GBE could increase the relaxant potency of mirodenafil even at a minimally effective dose. The K flow through potassium channels might be one of the mechanisms involved in this synergistic relaxation. © 2011 AJA, SIMM &SJTU. All rights reserved.