Involvement of potassium channels in the protective effect of 17β-estradiol on hypercholesterolemic rabbit carotid artery

The involvement of endothelium-derived hyperpolarizing factor (EDHF) in the protective effect of 17β-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+17β-estradiol; standard chow+1% cholesterol, cholesterol group; or (cholesterol+estradiol) group, 1% cholesterol chow+17β-estradiol. Relaxations to acetylcholine (ACh) (3 nM–30 μM) were performed with N nitro- -arginine methyl ester (300 μM) and indomethacin (10 μM). Charybdotoxin (50 nM)+apamin (50 nM), glibenclamide (10 μM) 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 17β-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 μM), a nitric oxide scavenger, or by LY83183 (10 μM), a guanylate cyclase inhibitor. Thus, in the rabbit carotid artery, the protective effect of 17β-estradiol against hypercholesterolemia is probably mediated by a nitric oxide/cyclic GMP pathway which activates calcium-targeted and ATP-dependent K+ channels.