title: Mechanisms of nitric oxide-independent relaxations induced by carbachol and acetylcholine in rat isolated renal arteries.
abstract: 1. In rat isolated renal artery segments contracted with 0.1 microM phenylephrine and in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), carbachol and acetylcholine produced endothelium-dependent relaxations. The mechanisms underlying these relaxations were studied. 2. These relaxations were not affected by ODQ (1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one) or indomethacin. In arteries contracted with 20 - 30 mM K(+), L-NAME-resistant relaxations induced by carbachol and acetylcholine were virtually absent. 3. The Na(+)-K(+) ATPase inhibitor ouabain reduced these relaxations in a concentration-dependent manner. 4. In K(+)-free media, addition of K(+) (5 mM) produced 90. 5+/-3.9% (n=3) relaxation of phenylephrine-induced tone. This relaxation was endothelium-independent and ouabain-sensitive. 5. Tetraethylammonium (TEA), charybdotoxin (ChTX) and iberiotoxin (IbTX) reduced the sensitivity of carbachol-induced relaxations, but did not change the maximal response. These relaxations were not altered by 4-aminopyridine (4-AP), glibenclamide or apamin. Acetylcholine (1 microM)-induced relaxation was reduced by ChTX, but not by TEA or IbTX. 6. The cytochrome P450 inhibitor miconazole, but not 17-octadecynoic acid, reduced the sensitivity of carbachol-induced relaxations, without changing the maximal response. 7. In conclusion, in rat isolated renal arteries, acetylcholine and carbachol produced a non-NO/non-PGI(2) relaxation which is mediated by an endothelium-derived hyperpolarizing factor (EDHF). This factor does not appear to be a cytochrome P450 metabolite. The inhibition by ouabain of these relaxations suggests the possible involvement of Na(+)-K(+) ATPase activation in EDHF responses, although other mechanisms cannot be totally ruled out.
authors.affiliation: Pharmacology Research Group, Department of Medical Laboratory Science, RMIT University, Melbourne, Victoria, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.forename: C G
authors.initials: CG
authors.lastname: Li
authors.forename: M J
authors.initials: MJ
authors.lastname: Rand
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D065607:Cytochrome P-450 Enzyme Inhibitors; D010069:Oxadiazoles; D010455:Peptides; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D014662:Vasoconstrictor Agents; D018999:Charybdotoxin; D010656:Phenylephrine; D009569:Nitric Oxide; D010042:Ouabain; D019789:Tetraethylammonium; C064719:iberiotoxin; D008825:Miconazole; D002217:Carbachol; D000109:Acetylcholine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin