Critical role of gap junctions in endothelium-dependent hyperpolarization in rat mesenteric arteries.
1. Acetylcholine (ACh) evokes endothelium-dependent hyperpolarization in arterial cells, presumably through endothelium-derived hyperpolarizing factor (EDHF). The identity of EDHF is still elusive; however, several recent studies suggest the possible involvement of myoendothelial gap junctions in the EDHF response. 2. To elucidate the role of gap junctions in endothelium-dependent hyperpolarization, we examined the effects of the gap junction inhibitors 18 alpha-glycyrrhetinic acid (18 alpha-GA; 10(-4) mol/L) and carbenoxolone (3 x 10(-4) mol/L), a water-soluble form of 18 beta-GA, on hyperpolarization and relaxation to ACh in rat proximal and distal mesenteric arteries. Experiments were performed in the presence of indomethacin (10(-5) mol/L) and N(G)-nitro-L-arginine (10(-4) mol/L). 3. In both proximal and distal mesenteric arteries, ACh-induced hyperpolarization and relaxation were partially inhibited by 18 alpha-GA and abolished by carbenoxolone. 4. Endothelium-independent hyperpolarization to levcromakalim, an ATP-sensitive K+ channel opener, were unaffected by 18 alpha-GA or carbenoxolone in both arteries. 5. Relaxations to levcromakalim were unaffected by 18 alpha-GA, but were inhibited somewhat by carbenoxolone in proximal mesenteric arteries. 6. These findings suggest that myoendothelial gap junctions play a critical role in EDHF-mediated responses in both proximal and distal mesenteric arteries of the rat.
Goto
Kenichi
K
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Fujii
Koji
K
Kansui
Yasuo
Y
Abe
Isao
I
Iida
Mitsuo
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D002229:Carbenoxolone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; C119129:18alpha-glycyrrhetinic acid; D002229:Carbenoxolone; D000109:Acetylcholine; D006034:Glycyrrhetinic Acid