title: Involvement of potassium channels in the protective effect of 17beta-estradiol on hypercholesterolemic rabbit carotid artery.
abstract: The involvement of endothelium-derived hyperpolarizing factor (EDHF) in the protective effect of 17beta-estradiol was investigated on the phenylephrine-precontracted carotid artery from cholesterol fed rabbits. Animals were fed for 8 weeks as follows: control group, standard chow; (control+estradiol) group, standard chow+17beta-estradiol; standard chow+1% cholesterol, cholesterol group; or (cholesterol+estradiol) group, 1% cholesterol chow+17beta-estradiol. Relaxations to acetylcholine (ACh) (3 nM-30 microM) were performed with N(omega) nitro-L-arginine methyl ester (300 microM) and indomethacin (10 microM). Charybdotoxin (50 nM)+apamin (50 nM), glibenclamide (10 microM) or 4-aminopyridine (1 mM) were used to block, respectively, calcium-activated-K(+), adenosine triphosphate (ATP)-sensitive-K(+) and voltage-dependent K(+) channels. In the control group, ACh induced a residual concentration-dependent relaxation. This response was impaired by hypercholesterolemia and restored by 17beta-estradiol. In control and cholesterol groups, 4-aminopyridine or glibenclamide did not affect this relaxation, but in (control+estradiol) and (cholesterol+estradiol) groups, glibenclamide suppressed it. In all groups, this persisting relaxation was completely abolished by charybdotoxin alone or with apamin, by hemoglobin (10 microM), a nitric oxide scavenger, or by LY83183 (10 microM), a guanylate cyclase inhibitor. Thus, in the rabbit carotid artery, the protective effect of 17beta-estradiol against hypercholesterolemia is probably mediated by a nitric oxide/cyclic GMP pathway which activates calcium-targeted and ATP-dependent K(+) channels.
authors.affiliation: Laboratoire de Pharmacologie, Faculté de Pharmacie, 2 rue du Dr Marcland, 87025 cédex, Limoges, France. oudart@unilim.fr
authors.forename: K
authors.initials: K
authors.lastname: Ghanam
authors.forename: L
authors.initials: L
authors.lastname: Ea-Kim
authors.forename: J
authors.initials: J
authors.lastname: Javellaud
authors.forename: N
authors.initials: N
authors.lastname: Oudart
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001685:Biological Factors / Q000032:analysis / Q000096:biosynthesis*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D046508:Culture Techniques; D004195:Disease Models, Animal; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood* / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011336:Probability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D001685:Biological Factors; D015221:Potassium Channels; C067410:endothelium-dependent hyperpolarization factor; D004958:Estradiol; D002784:Cholesterol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester