title: Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms.
abstract: OBJECTIVE
  To investigate the mechanisms underlying the vasorelaxant effect of formononetin, an O-methylated isoflavone, in isolated arteries, and its antihypertensive activity in vivo.
  
  
  METHODS
  Arterial rings of superior mesenteric arteries, renal arteries, cerebral basilar arteries, coronary arteries and abdominal aortas were prepared from SD rats. Isometric tension of the arterial rings was recorded using a myograph system. Arterial pressure was measured using tail-cuff method in spontaneously hypertensive rats.
  
  
  RESULTS
  Formononetin (1-300 μmol/L) elicited relaxation in arteries of the five regions that were pre-contracted by KCl (60 mmol/L), U46619 (1 μmol/L) or phenylephrine (10 μmol/L). The formononetin-induced relaxation was reduced by removal of endothelium or by pretreatment with L-NAME (100 μmol/L). Under conditions of endothelium denudation, formononetin (10, 30, and 100 μmol/L) inhibited the contraction induced by KCl and that induced by CaCl(2) in Ca(2+)-free depolarized medium. In the absence of extracellular Ca(2+), formononetin (10, 30, and 100 μmol/L) depressed the constriction caused by phenylephrine (10 μmol/L), but did not inhibit the tonic contraction in response to the addition of CaCl(2) (2 mmol/L). The contraction caused by caffeine (30 mmol/L) was not inhibited by formononetin (100 μmol/L). Formononetin (10 and 100 μmol/L) reduced the change rate of Ca(2+)-fluorescence intensity in response to KCl (50 mmol/L). In spontaneously hypertensive rats, formononetin (5, 10, and 20 mg/kg) slowly lowered the systolic, diastolic and mean arterial pressure.
  
  
  CONCLUSIONS
  Formononetin causes vasodilatation via two pathways: (1) endothelium-independent pathway, probably due to inhibition of voltage-dependent Ca(2+) channels and intracellular Ca(2+) release; and (2) endothelium-dependent pathway by releasing NO. Both the pathways may contribute to its antihypertensive effect.
authors.affiliation: Department of Pharmacolgy, Xi-an Jiaotong University College of Medicine, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Yong-xiao
authors.initials: YX
authors.lastname: Cao
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D007529:Isoflavones; D014665:Vasodilator Agents; C007768:formononetin