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 microM norepinephrine, in a dose-dependent manner with an IC50 of 50 micrograms/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 microM)-induced relaxation of norepinephrine-induced precontraction ofendothelium-denuded rings, with an IC50 of 20 micrograms/mL. In serotonin-contracted rings, TJ-12 caused slight, though statistically significant, relaxation only at high doses (> 200 micrograms/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.
Wei
M J
MJ
Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
Shintani
F
F
Kanba
S
S
Yagi
G
G
Asai
M
M
Kato
R
R
Nakaki
T
T
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D007564:Japan; D008297:Male; D008419:Materia Medica / Q000008:administration & dosage / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D008419:Materia Medica; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D012701:Serotonin; D011188:Potassium; D009638:Norepinephrine