title: Butylidenephthalide antagonizes cromakalim-induced systolic pressure reduction in conscious normotensive rats.
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 Ca(2+) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Taipei Medical University Hospital, 252 Wu-Hsing St., Taipei, 110, Taiwan.
authors.forename: Chung-Hung
authors.initials: CH
authors.lastname: Shih
authors.affiliation: Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei, 110, Taiwan.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei, 110, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei, 110, Taiwan. wc_ko@tmu.edu.tw.
authors.forename: Wun-Chang
authors.initials: WC
authors.lastname: Ko
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019806:Cromakalim / Q000009:adverse effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D015394:Molecular Structure; D010796:Phthalic Anhydrides / Q000008:administration & dosage* / Q000737:chemistry; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D007004:Hypoglycemic Agents; D010796:Phthalic Anhydrides; D015221:Potassium Channels; D019806:Cromakalim; C026105:butylidenephthalide