Butylidenephthalide antagonizes cromakalim-induced systolic pressure reduction in conscious normotensive rats

Chung Hung Shih, Yu Jing Lin, Chi Ming Chen, Wun-Chang Ko

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Butylidenephthalide (Bdph), a main constituent of Ligusticum chuanxiong Hort., was reported to have selective antianginal effect without changing blood pressure in conscious rat. Recently, we have observed that Bdph antagonized cromakalim, an ATP-dependent K+ channel opener, in guinea-pig trachea. Thus, we were interested in investigating whether Bdph at the dose without changing blood pressure antagonized cromakalim-induced systolic pressure reduction in conscious rats. Methods: Systolic arterial pressures of conscious rats were determined by using the indirect tail-cuff method. Results: Bdph (30 mg/kg, i.p.) did not affect baseline systolic pressure in conscious normotensive and spontaneous hypertensive rats. Bdph (30 mg/kg, i.p.) also did not affect log dose-response curves of prazosin, clonidine and Bay K 8644, a Ca2+ channel activator, in normotensive rats. However, Bdph (30 mg/kg, i.p.) similar to 4-aminopyridine (4-AP, 0.4 mg/kg, i.p.), a K+ channel blocker, non-parallelly but surmountably, and partially similar to glibenclamide (GBC, 10 mg/kg, i.v.), an ATP-sensitive K+ channel blocker, surmountably but not parallelly rightward shifted the log dose-systolic pressure reduction curve of cromakalim, an ATP-sensitive K+ channel opener, in normotensive rats, respectively. Discussion: The antagonistic effect of Bdph against cromakalim was similar to that of 4-AP, a K+ channel blocker of Kv1 family, and partially similar to that of GBC, an ATP-sensitive K+ channel blocker. Thus, Bdph may be a kind of K+ channel blockers, which have been reviewed to have a potential clinical use for Alzheimer disease. Indeed, Bdph has also been reported to reverse the deficits of inhibitory avoidance performance and improve memory in rats. Recently, 4-AP was reported to treat Episodic ataxia type 2 (EA2) which is a form of hereditary neurological disorder. Consistently, Bdph was recently reported to have antihyperglycemic activity in mice, since GBC is a powerful oral hypoglycemic drug. Conclusions: Bdph similar to 4-AP and partially similar to GBC may block Kv1 family and ATP-sensitive K+ channels in conscious normotensive rats.

Original languageEnglish
Article number344
JournalBMC Complementary and Alternative Medicine
Volume15
Issue number1
DOIs
Publication statusPublished - Oct 5 2015

Keywords

  • 4-Aminopiridine
  • ATP-sensitive K channels
  • Butylidenephthalide
  • Conscious normotensive rats
  • Cromakalim
  • K1 family of K channels

ASJC Scopus subject areas

  • Complementary and alternative medicine

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