The involvement of K+ channels and the possible pathway of EDHF in the rabbit femoral artery.
10.3349/ymj.1999.40.4.331
- Author:
Seong Chun KWON
1
;
Wook Bum PYUN
;
Gi Young PARK
;
Hee Kyung CHOI
;
Kwang Se PAIK
;
Bok Soon KANG
Author Information
1. Department of Physiology, Yonsei University College of Medicine, Seoul, Korea. skwon@yumc.yonsei.ac.kr
- Publication Type:Original Article ; In Vitro ; Research Support, Non-U.S. Gov't
- Keywords:
Rabbit femoral artery;
endothelium-dependent relaxation;
acetylcholine;
EDHF;
K+ channel
- MeSH:
Acetylcholine/pharmacology;
Animal;
Biological Factors/physiology*;
Female;
Femoral Artery/physiology*;
Femoral Artery/drug effects;
In Vitro;
Male;
Potassium Channels/physiology*;
Rabbits;
Vasodilation/physiology;
Vasodilator Agents/pharmacology
- From:Yonsei Medical Journal
1999;40(4):331-338
- CountryRepublic of Korea
- Language:English
-
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.
