Homocysteine impairs estrogen-induced vasodilation in isolated rat arterioles.
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.
Smolders
Raimond G V
RG
"Aging Women" Project, Institute for Cardiovascular Research, Vrije University, Amsterdam, The Netherland.
Sipkema
Pieter
P
Kenemans
Peter
P
Stehouwer
Coen D A
CD
Van Der Mooren
Marius J
MJ
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
D004791:Enzyme Inhibitors; D006710:Homocysteine; D019335:Nitroarginine; D004958:Estradiol