title: The involvement of K+ channels and the possible pathway of EDHF in the rabbit femoral artery.
abstract: Experiments were designed to characterize the cellular mechanisms of action of endothelium-derived vasodilator substances in the rabbit femoral artery. Acetylcholine (ACh, 10(-8)-10(-5) M) induced a concentration-dependent relaxation of isolated endothelium-intact arterial rings precontracted with norepinephrine (NE, 10(-6) M). The ACh-induced response was abolished by the removal of endothelium. NG-nitro-L-arginine (L-NAME, 10(-4) M), an inhibitor of NO synthase, partially inhibited ACh-induced endothelium-dependent relaxation, whereas indomethacin (10(-5) M) showed no effect on ACh-induced relaxation. 25 mM KCl partially inhibited ACh-induced relaxation by shifting the concentration-response curve and abolished the response when combined with L-NAME and NE. In the presence of L-NAME, ACh-induced relaxation was unaffected by glibenclamide (10(-5) M) but significantly reduced by apamin (10(-6) M), and almost completely blocked by tetraethylammonium (TEA, 10(-3) M), iberiotoxin (10(-7) M) and 4-aminopyridine (4-AP, 5 x 10(-3) M). The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10(-5) M) and miconazole (10(-5) M) also significantly inhibited ACh-induced relaxation. Ouabain (10(-6) M), an inhibitor of Na+, K(+)-ATPase, or K(+)-free solution, also significantly inhibited ACh-induced relaxation. ACh-induced relaxation was not significantly inhibited by 18-alpha-glycyrrhetinic acid (18 alpha-GA, 10(-4) M). These results of this study indicate that ACh-induced endothelium-dependent relaxation of the rabbit femoral artery occurs via a mechanism that involves activation of Na+, K(+)-ATPase and/or activation of both the voltage-gated K+ channel (Kv) and the large-conductance, Ca(2+)-activated K+ channel (BKCa). The results further suggest that EDHF released by ACh may be a cytochrome P450 product.
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul, Korea. skwon@yumc.yonsei.ac.kr
authors.forename: S C
authors.initials: SC
authors.lastname: Kwon
authors.forename: W B
authors.initials: WB
authors.lastname: Pyun
authors.forename: G Y
authors.initials: GY
authors.lastname: Park
authors.forename: H K
authors.initials: HK
authors.lastname: Choi
authors.forename: K S
authors.initials: KS
authors.lastname: Paik
authors.forename: B S
authors.initials: BS
authors.lastname: Kang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D015221:Potassium Channels; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D000109:Acetylcholine