Vasodilator effects of des(alpha-carboxy-3,4-dihydroxyphenethyl)lithospermic acid (8-epiblechnic acid), a derivative of lithospermic acids in salviae miltiorrhizae radix.

A potent vasodilator substance (compound III), [alpha]D +141 degrees, was isolated from salviae miltiorrhizae radix (dan-shen). This substance was determined to be des(alpha-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 Ca(2+)-induced contracture of depolarized aortic strips with isotonic high K+ (60 nM) were not affected by comp. III. Ca(2+)-induced contraction of aortic strips, preincubated with 10(-6) M NE in the presence of 10(-6) M nicardipine and 0.01 mM EGTA in Ca(2+)-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.