Effects of agents that inactivate free radical NO (NO*) on nitroxyl anion-mediated relaxations, and on the detection of NO* released from the nitroxyl anion donor Angeli's salt.
1. The effects of agents that inactivate free radical nitric oxide (carboxy-PTIO, hydroxocobalamin and pyrogallol) were tested on relaxations produced by the nitroxyl anion (NO(-)) donor Angeli's salt in rat aortic rings and anococcygeus muscles. The amount of NO(*) generated from Angeli's salt in the presence of these agents was measured using a NO(*)-selective electrode sensor. 2. Carboxy-PTIO (100, 300 microM), hydroxocobalamin (30, 100 microM) and pyrogallol (10, 30 microM) significantly reduced relaxations produced by Angeli's salt (0.3 microM) in aortic rings but not in anococcygeus muscles. 3. NO(*) generated from Angeli's salt (0.1 - 10 microM), as detected by the sensor electrode, was less than 0.5% of the amount of Angeli's salt added. Carboxy-PTIO (100 microM) and hydroxocobalamin (30 microM), but not pyrogallol significantly increased the amount of NO(*) detected. 4. In the presence of an oxidizing agent copper [II] (as CuSO(4) 100 microM), the amount of NO(*) detected from 0.3 microM of Angeli's salt increased from an undetectable level of 142.7+/-15.7 nM (equivalent to 47.6% of Angeli's salt added). Under these conditions, carboxy-PTIO, hydroxocobalamin and pyrogallol significantly reduced the amount of NO(*) detected from Angeli's salt as well as the signal generated by an equivalent amount of authentic NO (0.33 microM). 5. The difference in effects of these agents on relaxations to Angeli's salt in the aorta and the anococcygeus muscle may be explained by the ready conversion of NO(-) to NO(*) in the aorta through an unidentified mechanism, which makes NO(-) susceptible to inactivation by these agents. Furthermore, in addition to inactivating NO(*), carboxy-PTIO and hydroxocobalamin may themselves oxidize NO(-) to NO(*), albeit slightly.
Ellis
A
A
Drug Research & Development Group, School of Medical Sciences, RMIT University, P.O. Box 71, Bundoora West, Victoria 3083, Australia.
Lu
H
H
Li
C G
CG
Rand
M J
MJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D006397:Hematinics / Q000494:pharmacology; D006879:Hydroxocobalamin / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D011748:Pyrogallol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D001565:Benzoates; D005609:Free Radicals; D006397:Hematinics; D007093:Imidazoles; D009573:Nitrites; D009589:Nitrogen Oxides; D011748:Pyrogallol; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; C021229:oxyhyponitrite; D009569:Nitric Oxide; C039900:nitroxyl; D006879:Hydroxocobalamin