Endothelium-dependent and-independent vasoactive actions of a japanese kampo medicine, saiko-ka-ryukotsu-borei-to

Saiko-ka-ryukotsu-borei-to (TJ-12) is a Japanese kampo medicine used clinically for the treatment of hypertension and atherosclerosis. We investigated the effects of TJ-12 on the contraction of rat thoracic aorta induced by norepinephrine, 5-hydroxytryptamine and high potassium. TJ-12 relaxed endothelium-denuded rings, which had been precontracted with 1 μM norepinephrine, in a dose-dependent manner with an IC50 of 50 μg/mL. However, in the presence of TJ-12, endothelium-intact rings initially showed enhanced norepinephrine-induced contraction, followed by relaxation. Interestingly, TJ-12 dose-dependently reversed nitric oxide (2 μM)-induced relaxation of norepinephrine-induced precontraction ofendothelium-denuded rings, with an IC50 of 20 μg/mL. In serotonin-contracted rings, TJ-12 caused slight, though statistically significant, relaxation only at high doses (> 200 μg/mL). In constrat to these receptor-mediated contractions. TJ-12 failed to affect the tension produced by high potassium 40 mM). These results suggest that the antihypertensive effects of TJ-12 could be related to inhibition of norepinephrine-induced vasoconstriction. In addition, our in vitro experiments revealed an inhibitory effect on nitric oxide-induced relaxation.