title: Field stimulation-induced tetrodotoxin-resistant vasorelaxation is mediated by sodium hypochlorite.
abstract: This study was done to determine the mechanism of field stimulation-induced tetrodotoxin (TTX)- and NG- nitro-l-arginine (LNA)-resistant vasorelaxation. Field stimulation with platinum and carbon, but not with silver, electrodes (30 V, 30 HZ, 2-5 ms pulse width) as well as electrically stimulated salt (0.9% NaCl) solution (ESSS) or Krebs solution caused 100% relaxation of phenylephrine-contracted rat aortic strips, which was TTX and LNA resistant and endothelium independent. ESSS also relaxed other vascular preparations (rabbit aorta and renal artery, dog coronary artery, pig ductus arteriosus, and rat portal vein). The electric current generated hypochlorite (OCl-) and H2O2 from the salt solution; however, vasorelaxation was caused by NaOCl and not by H2O2. ESSS and NaOCl caused contraction failure of spontaneously beating right atria of rats and did not affect uterine contractions, vascular cAMP, cGMP, or the pH of the tissue bath. Field stimulation, ESSS, and NaOCl did not relax aortic preparations contracted by 32 mmol/L potassium and their vasorelaxant effects on phenylephrine-contracted rat aortic strips and rings were completely reversed by tetraethylammonium and partially by glibenclamide and iberiotoxin. We conclude that electric pulses generate the oxidant OCl- from the salt solution, which causes vasorelaxation by increasing K+ conductance.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada. daya.varma@mcgill.ca
authors.forename: Daya R
authors.initials: DR
authors.lastname: Varma
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Xia
authors.forename: Mehran
authors.initials: M
authors.lastname: Ozgoli
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.forename: Shree
authors.initials: S
authors.lastname: Mulay
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D016877:Oxidants / Q000378:metabolism; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D012965:Sodium Chloride / Q000737:chemistry; D012973:Sodium Hypochlorite / Q000378:metabolism* / Q000494:pharmacology; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D016877:Oxidants; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D014665:Vasodilator Agents; D013779:Tetrodotoxin; D012965:Sodium Chloride; D006861:Hydrogen Peroxide; D012973:Sodium Hypochlorite; D011188:Potassium