[17B-estradiol and hypercholesterolemia: involvement of nitric oxide].
The mechanisms of the protective effect of 17B-estradiol were investigated in the middle cerebral artery (MCA) and aorta isolated from cholesterol-fed rabbits. Three groups were assigned: control group (standard chow), cholesterol group (standard chow+1% cholesterol) and estradiol group (1% cholesterol+17B-estradiol). The MCA and the aorta were isolated, precontracted respectively with high K(+) solution or with phenylephrine and exposed to cumulative acetylcholine concentrations. In the control group, acetylcholine induced a concentration-dependent relaxation in the aorta and the MCA. Cholesterol diet for eight months reduced significantly the maximal response to acetylcholine by about 50% in the aorta and by about 30% in the MCA. The chronic treatment with 17B-estradiol restored this impaired relaxations to acetylcholine. Incubation of arteries from estradiol group with N(omega)-nitro L-arginine methyl-ester (L-NAME), a potent inhibitor of constitutive nitric oxide synthase, entirely abolished the relaxation to acetylcholine while aminoguanidine, a potent inhibitor of inducible nitric oxide synthase, did not affect this relaxation. These observations suggest that the protective effect of 17B-estradiol against hypercholesterolemia is mediated via a release of endothelial nitric oxide.
Ghanam
K
K
Laboratoire de Pharmacologie, Faculté de Pharmacie, 2, rue du Dr Marcland, F 87025 Limoges Cedex.
Javellaud
J
J
Ea-Kim
L
L
Oudart
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000494:pharmacology* / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D006937:Hypercholesterolemia; D066298:In Vitro Techniques; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; D004958:Estradiol; D002784:Cholesterol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester