Vasodilator Effects of Des (α-carboxy-3, 4-dihydroxyphenethyl) lithospermic Acid (8-Epiblechnic Acid), a Derivative of Lithospermic Acids in Salviae Miltiorrhizae Radix

抄録

A potent vasodilator substance (compound III), [α]_D +141°, was isolated from salviae miltiorrhizae radix (dan-shen). This substance was determined to be des (α-carboxy-3, 4-dihydroxyphenethyl) lithospermic acid on the basis of spectrometric and chemical evidence, and was identified with an authentic sample of 8-epiblechnic acid. However, comp. III seemed to be formed from lithospermic acid (LSA) and LSA-B during a chemical procedure to separate active ingredients. It caused a sustained, slowly developing relaxation of rat aortic strips precontracted with norepinephrine (NE) in preparations with or without endothelium. The NE-induced concentration-dependent contraction of aortic strips was significantly attenuated by pretreatment with comp. III. Concentration-response curves for Ca²⁺-induced contracture of depolarized aortic strips with isotonic high K⁺ (60mM) were not affected by comp. III. Ca²⁺-induced contraction of aortic strips, preincubated with 10^-6M NE in the presence of 10^-6M nicardipine and 0.01mM EGTA in Ca²⁺-free solution, was slightly inhibited by comp. III. Pretreatment of aortic strips with comp. III slightly inhibited the phorbol ester (PMA)-induced contraction. These results suggest that comp. III inhibits NE-induced contraction of the aortic strips through reduction in Ca²⁺ mobilization. Since comp. III inhibits NE-induced sustained contraction, this agent may be useful in the treatment of hypertension.