Characterization of nitric oxide- and prostaglandin-independent relaxation in response to acetylcholine in rabbit renal artery.
1. We investigated the characterization of acetylcholine (ACh)-induced NG-nitro-L-arginine methyl ester (L-NAME)- and indomethacin (IND)-resistant relaxations, which can be mediated by endothelium-derived hyperpolarizing factor (EDHF), in rabbit renal arterial rings. 2. The relaxations were inhibited by SKF 525A, a cytochrome P450 inhibitor, but were not affected by other inhibitors, namely clotrimazole, 17-octadecynoic acid and alpha-naphthoflavone. Furthermore, 11,12-epoxyeicosatrienoic acid, a cytochrome P450 metabolite, did not relax arterial rings. 3. Arterial relaxations were significantly attenuated by charybdotoxin and iberiotoxin, but not by apamin, all K+ channel blockers. 4. In a sandwich bioassay experiment, ACh-induced L-NAME- and IND-resistant relaxations were not transferred to the detector site. 5. Relaxations were also significantly attenuated by 1-heptanol and 18 alpha-glycyrrhetinic acid, gap junctional coupling inhibitors. 6. These results indicate that, in the rabbit renal artery, L-NAME- and IND-resistant relaxations are mediated by factors other than cytochrome P450-derived arachidonic acid metabolites, which may be able to diffuse into the lumen but be partly transferred via myoendothelial gap junctions to adjacent vascular smooth muscle cells and relax muscles by opening high-conductance Ca(2+)-activated K+ channels.
Kagota
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nishinomiya, Japan. skagota@mwu.mukogawa-u.ac.jp
Yamaguchi
Y
Y
Nakamura
K
K
Kunitomo
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D026902:Potassium Channel Blockers; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001685:Biological Factors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D011453:Prostaglandins; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin