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Influence of redox compounds on nitrovasodilator‐induced relaxations of rat coronary arteries
Author(s) -
Murphy Michael E
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702777
Subject(s) - chemistry , ferricyanide , dithiothreitol , potency , ferrocyanide , nitric oxide , glutathione , redox , biochemistry , biophysics , inorganic chemistry , in vitro , organic chemistry , enzyme , biology , electrode
Various classes of nitrovasodilators release nitric oxide (NO) through distinct reaction pathways, many of which involve endogenous reductants and/or oxidants. This study examined relaxations of isolated rat coronary arteries induced by spermine NONOate (SPNO), 3‐morpholinosydnonimine (SIN‐1), nitroprusside (NP), S‐nitroso‐N‐acetylpenicillamine (SNAP) and nitroglycerin (NTG) in order to assess whether their potency was influenced by any of six redox compounds: 1 m M ascorbate, 1 m M dehydroascorbate, 0.1 m M dithiothreitol, 10 μ M diamide, 0.1 m M ferrocyanide, and 0.1 m M ferricyanide. Only SPNO spontaneously generated NO at measurable levels. These levels were decreased by the presence of ascorbate and dithiothreitol, which likewise decreased the potency of SPNO. The potency of SIN‐1 was unaffected by any redox compound except ferricyanide, which increased the potency not only of SIN‐1, but also of other nitrovasodilators and NO‐independent vasodilators. The potency of NP was decreased by two structurally similar multivalent anions, ferrocyanide and ferricyanide, suggesting that NP metabolism requires ionic binding to tissue. SNAP lost its potency in solutions containing ascorbate or dehydroascorbate. SNAP potency was also decreased by the glutathione oxidant, diamide, and by ferrocyanide and ferricyanide, suggesting that glutathione and ionic binding may be required for NO release. NTG appeared to relax arteries via two pathways. One required only low concentrations of NTG and a labile endogenous factor that was preserved by dithiothreitol and eliminated by ferricyanide. A distinct second pathway required higher concentrations of NTG. These distinct attributes of nitrovasodilator metabolism may underlie differences in regional specificity or tolerance development, and therefore might eventually be exploited in the development and use of nitrovasodilators.British Journal of Pharmacology (1999) 128 , 435–443; doi: 10.1038/sj.bjp.0702777