Butylidenephthalide 在離體狗血管的鬆弛作用
Relaxant Effects of Butylidenephthalide in Isolated Dog Blood Vessels
英文摘要
(1) Butylidenephthalide (Bdph) concentraction-dependently relaxed the isolated dog saphenous vein (SV), coronary artery (CA), femoral artery (FA) and mesentric artery (MA),
precontracted by KCl (60 mM) and phenylephrine (phe, 5 μM) with an exception of CA by prostaglandin F2α (PGF2α, 2 μM) instead of phe. The potency order of Bdph to these blood vessels was SV>
CA>FA, MA. There was a significant difference among these four tissues with an exception between FA and MA.
(2) Bdph also non-competitively inhibited cumulative KCl (5-120 mM)- and phe (0.1-100 μM)-induced contractions in these four blood vessels excluding CA to phe. Roughly, the potency order of Bdph to these blood vessels roughly was SV, CA>FA, MA. There was a significant difference between the former two and the latter
two, though no significant differences found between the former two and between the latter two.
(3) There was also no significant difference between -logIC50 and PD2' values in each tissue. It suggests that inhibitory effects of Bdph on Ca2+-influx through voltage (VOC) and/or receptor operated calcium channels (ROC) may be similar to those on Ca2+-release from calcium stores in each tissue. Bdph also non-competitively inhibited cumulative Ca2+-induced contractions in depolarized preparations. The potency order was SV>CA>FA, MA.
(4) The relaxing effects of Bdph was endothelium independent.
There was no correlation to opening of ATP- and/or Ca2+- sensitive potassium channels and to activation of adenylate and/
or guanylate cyclase.
(5) Bdph dose-dependently and parallelly leftward shifted the log dose-response curve of forskolin (FK) in SV or CA, and reduced the IC50 of FK. Bdph parallelly leftward shifted the log
dose-response curves of sodium nitroprusside (SNP) in CA or FA and reduced the IC50 of SNP. Bdph (200 μM) significantly enhanced the cAMP content in SV, Bdph (500 μM) significantly enhanced the cAMP and cGMP contents in CA, and Bdph (1000 μM) significantly enhanced cGMP content in FA. These results suggest that relaxant fect of Bdph may be related to inhibiting cAMP- dependent phosphodiesterase (PDE) activity in SV or CA and to inhibiting cGMP-dependent PDE activity in CA or FA.
(6) The above results suggest that the higher selectivities of
Bdph to SV and CA than to FA and MA, after Bdph administration in vivo, the reduction in venoreturn and the increase in
coronary flow may occur without affecting FA and MA. Therefore Bdph may be useful in the treatment of angina pectoris without affecting blood pressure. Further studies are needed to
elucidate its action mechanisms.
Key words: Butylidenephthalide, dog blood vessels, Ca2+ influx, Ca2+ release, cAMP-
dependent phosphodiesterase, cGMP-dependent phosphodiesterase