title: Homocysteine impairs estrogen-induced vasodilation in isolated rat arterioles.
abstract: OBJECTIVE
  Clinical and basic studies have provided evidence that the cardiovascular protective effects of estrogens are partly due to effects on vasoreactivity and changes in homocysteine metabolism. Moreover, homocysteine has also been shown to influence vasoreactivity. We investigated the influence of homocysteine on the rapid vasodilatory effects of estradiol in an isolated vessel setup.
  
  
  METHODS
  Isolated, spontaneously constricted, gracilis muscle arterioles (diameter approximately 50 micromol/L) from female Wistar rats were cumulatively exposed to 10-10 to 10-4 mol/L 17beta-estradiol in the presence of 50 micromol/L homocysteine or N-nitro-L-arginine (L-NA) (a blocker of nitric oxide synthesis), or both. Control experiments were done without L-NA or homocysteine (n = 6 for each series).
  
  
  RESULTS
  The dose-dependent dilation during short-term exposure to 17beta-estradiol was significantly less or absent in arterioles where L-NA, homocysteine, or both were present. The addition of 50 micromol/L homocysteine significantly increased the spontaneous constriction by 6% to 10%.
  
  
  CONCLUSIONS
  We showed that a pathophysiological concentration of homocysteine increases the spontaneous arteriolar constriction and inhibits the 17beta-estradiol-induced, endothelium-mediated, rapid vasodilatory effect on muscle arterioles from the female rat. The endothelium-independent vasodilation remained unchanged.
authors.affiliation: "Aging Women" Project, Institute for Cardiovascular Research, Vrije University, Amsterdam, The Netherland.
authors.forename: Raimond G V
authors.initials: RG
authors.lastname: Smolders
authors.forename: Pieter
authors.initials: P
authors.lastname: Sipkema
authors.forename: Peter
authors.initials: P
authors.lastname: Kenemans
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Marius J
authors.initials: MJ
authors.lastname: Van Der Mooren
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D006710:Homocysteine; D019335:Nitroarginine; D004958:Estradiol