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Planta Med 2002; 68(11): 1004-1009
DOI: 10.1055/s-2002-35671
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Relaxant Effects of Butylidenephthalide in Isolated Dog Blood Vessels

Wun Chang Ko1 , Chao-Chiun Liao1 , Chih-Hsien Shih1 , Chien-Bang Lei1 , Chi-Ming Chen2
  • 1Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan, ROC
  • 2School of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC
Further Information

Publication History

Received: February 13, 2002

Accepted: June 29, 2002

Publication Date:
26 November 2002 (online)

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Abstract

We investigated the reason why butylidenephthalide (Bdph) can have an antianginal effect without changing blood pressure in conscious rats. Isolated dog coronary artery (CA), femoral vein (FV), femoral artery (FA), and mesenteric artery (MA) were used to evaluate the relaxant effects of Bdph. Bdph concentration-dependently relaxed isolated CA, FV, FA, and MA precontracted by KCl (60 mM) and phenylephrine (phe, 5 μM) with the exception that CA was precontracted by prostaglandin F2 α (PGF2 α, 2 μM) instead of phe. The potency order of Bdph to these blood vessels was FV > CA > FA ≥ MA. Bdph also concentration-dependently and non-competitively inhibited cumulative KCl (5 - 120 mM)- and phe (0.1 - 100 μM)-induced contractions in normal, and inhibited cumulative Ca2+-induced contractions in depolarized blood vessels. The potency order of Bdph to these blood vessels was FV ≅ CA > FA ≅ MA. Bdph (0.02 - 0.04 mM) concentration-dependently and leftward-shifted the log concentration-response curves in parallel and significantly increased the pD2 value of forskolin, but not nitroprusside in FV. Bdph (0.1 mM) did both in CA. Bdph (0.225 - 0.45 mM) did the opposite to that of nitroprusside, but not forskolin, in FA. Bdph (0.45 - 0.9 mM) did neither in MA. Bdph (0.1 - 1 mM) significantly inhibited cAMP- but not cGMP-PDE activities in these four blood vessels, suggesting that Bdph more selectively inhibited the former in these tissues. The above results suggest that the higher potencies of Bdph on FV and CA than on FA and MA, may be interpreted as the reason why Bdph is useful in the treatment of angina pectoris without changing blood pressure, after Bdph administration in vivo, because the venoreturn may be reduced and the coronary flow may be increased without affecting the arterioles, such as MA, the main determinant of blood pressure.

Abbreviations

Bdph:butylidenephthalide

Phe:phenylephrine

PGF2α:prostaglandin F2α

CA:coronary artery

FV:femoral vein

FA:femoral artery

MA:mesenteric artery

cAMP:adenosine 3′,5′-cyclic monophosphate

cGMP:guanosine 3′,5′-cyclic monophosphate

PDE:phosphodiesterase

Key words

Butylidenephthalide - dog blood vessels - Ca2+ influx - Ca2+ release - cAMP-phosphodiesterase - cGMP-phosphodiesterase - Ligusticum chuaxiong - Umbelliferae

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Prof. Wun-Chang Ko

Graduate Institute of Medical Sciences

Taipei Medical University

250 Wu-Hsing St., Taipei 110

Taiwan, ROC.

Email: wc_ko@tmu.edu.tw

Fax: +886-2-2377-7639

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