Effects of treatment with 17beta-estradiol on the hypercholesterolemic rabbit middle cerebral artery.
OBJECTIVE
The effects of acute and long-term treatment with 17beta-estradiol on the vasomotor responses of rabbit middle cerebral artery (RMCA) were investigated.


METHODS
For 8 weeks, male rabbits consumed standard chow (control group), standard chow+1% cholesterol (cholesterol group) or 1% cholesterol chow+17beta-estradiol (i.m. injection 700 microg per week) (estradiol group). The RMCA was precontracted with high K(+) solution and exposed to agonists.


RESULTS
Acute exposure to 17beta-estradiol strongly induced relaxation of the RMCA isolated from either control or cholesterol groups. This effect was endothelium independent. Incubation with 17beta-estradiol shifted the calcium contraction curve to the right. High cholesterol diet impaired the relaxation induced by acetylcholine and did not alter relaxation to sodium nitroprusside or to papaverine. Chronic treatment with 17beta-estradiol restored this impaired relaxation to acetylcholine. This protective effect of estradiol was significantly reduced in the presence of N(omega) nitro-L-arginine methyl ester, a constitutive nitric oxide-synthase inhibitor and was not modified in the presence of aminoguanidine, an inducible nitric oxide-synthase inhibitor. Neither tetrabutylammonium, a blocker of calcium-activated K(+) channels, nor glibenclamide, a blocker of ATP-sensitive K(+) channels, affected concentration-response to acetylcholine in the RMCA of the estradiol group, whereas 4-aminopyridine, a blocker of voltage-dependent K(+) channels strongly inhibited this relaxation.


CONCLUSIONS
These results suggest that acute effects of 17beta-estradiol in the RMCA is mediated through blockade of calcium entry into vascular smooth muscle cells, while chronic treatment with this hormone seems to be mediated by release of nitric oxide which activates voltage-dependent potassium channels.
Ghanam
K
K
Laboratoire de Pharmacologie pharmaceutique, Facult¿e de Pharmacie, 2, rue du Dr Marcland, 87025, Limoges, France.
Javellaud
J
J
Ea-Kim
L
L
Oudart
N
N
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects*; D002536:Cerebral Arteries / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D014666:Vasomotor System / Q000187:drug effects
D004958:Estradiol