Nitrite Regulates Hypoxic Vasodilation via Myoglobin-Dependent Nitric Oxide Generation
DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Totzeck, Matthias | |
dc.contributor.author | Hendgen-Cotta, Ulrike B. | |
dc.contributor.author | Luedike, Peter | |
dc.contributor.author | Berenbrink, Michael | |
dc.contributor.author | Klare, Johann P. | |
dc.contributor.author | Steinhoff, Heinz-Juergen | |
dc.contributor.author | Semmler, Dominik | |
dc.contributor.author | Shiva, Sruti | |
dc.contributor.author | Williams, Daryl | |
dc.contributor.author | Kipar, Anja | |
dc.contributor.author | Gladwin, Mark T. | |
dc.contributor.author | Schrader, Juergen | |
dc.contributor.author | Kelm, Malte | |
dc.contributor.author | Cossins, Andrew R. | |
dc.contributor.author | Rassaf, Tienush | |
dc.date.accessioned | 2021-12-23T16:21:27Z | - |
dc.date.available | 2021-12-23T16:21:27Z | - |
dc.date.issued | 2012 | |
dc.identifier.issn | 00097322 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/13879 | - |
dc.description.abstract | Background-Hypoxic vasodilation is a physiological response to low oxygen tension that increases blood supply to match metabolic demands. Although this response has been characterized for >100 years, the underlying hypoxic sensing and effector signaling mechanisms remain uncertain. We have shown that deoxygenated myoglobin in the heart can reduce nitrite to nitric oxide (NO center dot) and thereby contribute to cardiomyocyte NO center dot signaling during ischemia. On the basis of recent observations that myoglobin is expressed in the vasculature of hypoxia-tolerant fish, we hypothesized that endogenous nitrite may contribute to physiological hypoxic vasodilation via reactions with vascular myoglobin to form NO center dot. Methods and Results-We show in the present study that myoglobin is expressed in vascular smooth muscle and contributes significantly to nitrite-dependent hypoxic vasodilation in vivo and ex vivo. The generation of NO center dot from nitrite reduction by deoxygenated myoglobin activates canonical soluble guanylate cyclase/cGMP signaling pathways. In vivo and ex vivo vasodilation responses, the reduction of nitrite to NO center dot, and the subsequent signal transduction mechanisms were all significantly impaired in mice without myoglobin. Hypoxic vasodilation studies in myoglobin and endothelial and inducible NO synthase knockout models suggest that only myoglobin contributes to systemic hypoxic vasodilatory responses in mice. Conclusions-Endogenous nitrite is a physiological effector of hypoxic vasodilation. Its reduction to NO center dot via the heme globin myoglobin enhances blood flow and matches O-2 supply to increased metabolic demands under hypoxic conditions. (Circulation. 2012; 126: 325-334.) | |
dc.description.sponsorship | Deutsche Herzstiftung; German Cardiac Society; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [RA 969/4-2, Ke405/5-1]; Biotechnology and Biological Sciences Research Council, UKUK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC); National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HL098032, RO1HL096973, PO1HL103455]; Institute for Transfusion Medicine; Hemophilia Center of Western Pennsylvania; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL096973, R01HL098032, P01HL103455] Funding Source: NIH RePORTER; This work was supported by the Deutsche Herzstiftung (scholarship to Dr Totzeck). Dr Luedike was supported by a scholarship of the German Cardiac Society. Drs Rassaf and Kelm were supported by grants from the Deutsche Forschungsgemeinschaft (RA 969/4-2 and Ke405/5-1). Dr Rassaf is a Heisenberg professor of the Deutsche Forschungsgemeinschaft (RA969/7-1). Drs Cossins and Berenbrink received funding from the Biotechnology and Biological Sciences Research Council, UK. Drs Gladwin and Shiva received research support from National Institutes of Health grants R01HL098032, RO1HL096973, and PO1HL103455; Institute for Transfusion Medicine; and Hemophilia Center of Western Pennsylvania. | |
dc.language.iso | en | |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | |
dc.relation.ispartof | CIRCULATION | |
dc.subject | BLOOD | |
dc.subject | Cardiac & Cardiovascular Systems | |
dc.subject | Cardiovascular System & Cardiology | |
dc.subject | CYCLIC-GMP | |
dc.subject | hypoxic vasodilation | |
dc.subject | IN-VIVO | |
dc.subject | ISCHEMIA-REPERFUSION | |
dc.subject | MECHANISMS | |
dc.subject | myoglobin | |
dc.subject | nitrite | |
dc.subject | NO | |
dc.subject | OXYGEN | |
dc.subject | Peripheral Vascular Disease | |
dc.subject | REDUCTASE-ACTIVITY | |
dc.subject | SYNTHASE | |
dc.subject | VASCULAR SMOOTH-MUSCLE | |
dc.title | Nitrite Regulates Hypoxic Vasodilation via Myoglobin-Dependent Nitric Oxide Generation | |
dc.type | journal article | |
dc.identifier.doi | 10.1161/CIRCULATIONAHA.111.087155 | |
dc.identifier.isi | ISI:000306978200020 | |
dc.description.volume | 126 | |
dc.description.issue | 3 | |
dc.description.startpage | 325+ | |
dc.contributor.orcid | 0000-0002-5761-5968 | |
dc.contributor.orcid | 0000-0002-5888-0157 | |
dc.contributor.orcid | 0000-0001-7289-3459 | |
dc.contributor.orcid | 0000-0002-0813-5212 | |
dc.contributor.orcid | 0000-0003-0060-1052 | |
dc.contributor.researcherid | W-7519-2019 | |
dc.contributor.researcherid | C-1428-2009 | |
dc.contributor.researcherid | H-3791-2014 | |
dc.contributor.researcherid | L-7214-2014 | |
dc.identifier.eissn | 15244539 | |
dc.publisher.place | TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA | |
dcterms.isPartOf.abbreviation | Circulation | |
dcterms.oaStatus | Green Accepted, Bronze | |
crisitem.author.dept | FB 04 - Physik | - |
crisitem.author.deptid | fb04 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | StHe633 | - |
Seitenaufrufe
4
Letzte Woche
0
0
Letzter Monat
0
0
geprüft am 06.06.2024