title: Identification of free nitric oxide radicals in rat bone marrow: implications for progenitor cell mobilization in hypertension.
abstract: Nitric oxide (NO) has been implicated in matrix metallopeptidase 9 (MMP9)-dependent mobilization of hematopoietic stem and progenitor cells from bone marrow (BM). However, direct measurement of NO in the BM remained elusive due to its low in situ concentration and short lifetime. Using NO spin trapping and electron paramagnetic resonance (EPR) spectroscopy we give the first experimental confirmation of free NO radicals in rodent BM. NO production was quantified and attributed to enzymatic activity of NO synthases (NOS). Although endothelial NOS (eNOS) accounts for most (66%) of basal NO, we identified a significant contribution (23%) from inducible NOS (iNOS). Basal NO levels closely correlate with MMP9 bioavailability in BM of both hypertensive and control rats. Our observations support the hypothesis that inadequate mobilization of BM-derived stem and progenitor cells in hypertension results from impaired NOS/NO/MMP9 signalling in BM, a condition that may be corrected with pharmacological intervention.
authors.affiliation: Department of Nephrology and the Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. m.a.aleksinskaya@lumc.nl
authors.forename: Marina A
authors.initials: MA
authors.lastname: Aleksinskaya
authors.forename: Ernst E H
authors.initials: EE
authors.lastname: van Faassen
authors.forename: Jelly
authors.initials: J
authors.lastname: Nelissen
authors.forename: Ben J A
authors.initials: BJ
authors.lastname: Janssen
authors.forename: Jo G R
authors.initials: JG
authors.lastname: De Mey
authors.forename: Roeland
authors.initials: R
authors.lastname: Hanemaaijer
authors.forename: Ton
authors.initials: T
authors.lastname: Rabelink
authors.forename: Anton Jan
authors.initials: AJ
authors.lastname: van Zonneveld
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
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