1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. URL Address <a href="http://doi.org/10.1152/ajpheart.00436.2007" target="_blank" rel="noreferrer noopener">http://doi.org/10.1152/ajpheart.00436.2007</a> Pages H3720–3725 Issue 6 Volume 293 Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Redox-dependent coronary metabolic dilation. Publisher An entity responsible for making the resource available American journal of physiology. Heart and circulatory physiology Date A point or period of time associated with an event in the lifecycle of the resource 2007 2007-12 Subject The topic of the resource *Paracrine Communication; *Vasodilation/drug effects; Acetylcysteine/pharmacology; Animals; Antioxidants/pharmacology; Cardiac/drug effects/*metabolism; Conditioned/metabolism; Coronary Vessels/drug effects/enzymology/*metabolism; Culture Media; Dithiothreitol/pharmacology; Enzyme Activation; Fluorescence; Hydrogen Peroxide/metabolism; Imidazoles/pharmacology; In Vitro Techniques; Microscopy; Myocytes; Nitroprusside/pharmacology; Oxidation-Reduction; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism; Phosphorylation; Protein Kinase Inhibitors/pharmacology; Pyridines/pharmacology; Rats; Reactive Oxygen Species/*metabolism; Reducing Agents/pharmacology; Sulfhydryl Compounds/*metabolism; Vasodilator Agents/pharmacology; Wistar Creator An entity primarily responsible for making the resource Saitoh Shu-ichi; Kiyooka Takahiko; Rocic Petra; Rogers Paul A; Zhang Cuihua; Swafford Albert; Dick Gregory M; Viswanathan Chandrasekar; Park Yoonjung; Chilian William M Description An account of the resource We have observed that hydrogen peroxide (H2O2), the dismutated product of superoxide, is a coronary metabolic dilator and couples myocardial oxygen consumption to coronary blood flow. Because the chemical activity of H2O2 favors its role as an oxidant, and thiol groups are susceptible to oxidation, we hypothesized that coronary metabolic dilation occurs via a redox mechanism involving thiol oxidation. To test this hypothesis, we studied the mechanisms of dilation of isolated coronary arterioles to metabolites released by metabolically active (paced at 400 min) isolated cardiac myocytes and directly compared these responses with authentic H2O2. Studies were performed under control conditions and using interventions designed to reduce oxidized thiols [0.1 microM dithiothreitol (DTT) and 10 mM N-acetyl-L-cysteine (NAC)]. Aliquots of the conditioned buffer from paced myocytes produced vasodilation of isolated arterioles (peak response, 71% +/- 6% of maximal dilation), whereas H2O2 produced complete dilation (92% +/- 7%). Dilation to either the conditioned buffer or to H2O2 was significantly reduced by the administration of either NAC or DTT. The location of the thiols oxidized by the conditioned buffer or of H2O2 was determined by the administration of the fluorochromes monochlorobimane (20 microM) or monobromotrimethylammoniobimane (20 microM), which covalently label the reduced total or extracellular-reduced thiols, respectively. H2O2 or the conditioned buffer predominantly oxidized intracellular thiols since the fluorescent signal from monochlorobimane was reduced more than that of monobromotrimethylammoniobimane. To determine whether one of the intracellular targets of thiol oxidation that leads to dilation is the redox-sensitive kinase p38 mitogen-activated protein (MAP) kinase, we evaluated dilation following the administration of the p38 inhibitor SB-203580 (10 microM). The inhibition of p38 attenuated dilation to either H2O2 or to the conditioned buffer from stimulated myocytes by a similar degree, but SB-203580 did not attenuate dilation to nitroprusside. Western blot analysis for the activated form of p38 (phospho-p38) in the isolated aortae revealed robust activation of this enzyme by H2O2. Taken together, our results show that an active component of cardiac metabolic dilation, like that of H2O2, produces dilation by the oxidation of thiols, which are predominantly intracellular and dependent activation on the p38 MAP kinase. Thus coronary metabolic dilation appears to be mediated by redox-dependent signals. Identifier An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1152/ajpheart.00436.2007" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00436.2007</a> Rights Information about rights held in and over the resource Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s). *Paracrine Communication *Vasodilation/drug effects 2007 Acetylcysteine/pharmacology American journal of physiology. Heart and circulatory physiology Animals Antioxidants/pharmacology Cardiac/drug effects/*metabolism Chilian William M Conditioned/metabolism Coronary Vessels/drug effects/enzymology/*metabolism Culture Media Department of Integrative Medical Sciences Dick Gregory M Dithiothreitol/pharmacology Enzyme Activation Fluorescence Hydrogen Peroxide/metabolism Imidazoles/pharmacology In Vitro Techniques Kiyooka Takahiko Microscopy Myocytes NEOMED College of Medicine Nitroprusside/pharmacology Oxidation-Reduction p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism Park Yoonjung Phosphorylation Protein Kinase Inhibitors/pharmacology Pyridines/pharmacology Rats Reactive Oxygen Species/*metabolism Reducing Agents/pharmacology Rocic Petra Rogers Paul A Saitoh Shu-ichi Sulfhydryl Compounds/*metabolism Swafford Albert Vasodilator Agents/pharmacology Viswanathan Chandrasekar Wistar Zhang Cuihua