title: Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents.
abstract: NADPH oxidase-generated superoxide can modulate crucial intracellular signaling cascades in neurons of the nucleus tractus solitarius (NTS), a brain region that plays an important role in cardiovascular processes. Modulation of NTS signaling by superoxide may be linked to the subcellular location of the mobile NADPH oxidase p47(phox) subunit, which is known to be present in dendrites of NTS neurons. It is not known, however, if hypertension can produce changes in the trafficking of p47(phox) in defined NTS subregions, particularly the preferentially barosensitive dorsomedial NTS (dmNTS), or preferentially gastrointestinal medial NTS (mNTS). We used immunogold electron microscopy to determine if p47(phox) localization was differentially affected in dendritic profiles of neurons from these NTS subregions of the rat in response to distinct models of hypertension, namely chronic 7-day subcutaneous administration of angiotensin II (AngII), or phenylephrine. In small (<1 microm) dendritic processes, both AngII and phenylephrine produced a decrease in intracellular p47(phox) labeling selectively in dmNTS neurons. In intermediate-size (1-2 microm) dendritic profiles in the dmNTS region only, there was an increase in p47(phox) labeling in response to each hypertensive agent, although these changes occurred in different subcellular compartments. There was an increase in non-vesicular labeling in response to AngII, but an increase in surface labeling with phenylephrine. Moreover, each of the changes in p47(phox) targeting mentioned above occurred in dendritic profiles with, or without immunoperoxidase labeling for the AngII AT-1A receptor subtype (AT-1A). These results indicate that chronic administration of agents that induce hypertension can also produce changes in the subcellular localization in p47(phox) in dmNTS neurons. Thus, systemic hypertension may produce alterations in the trafficking of proteins associated with superoxide production in central autonomic neurons, thus revealing a potentially important neurogenic component of free radical production and systemic blood pressure elevation.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 411 E. 69th St., KB410, New York, NY 10021, USA. mjg2003@mail.med.cornell.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Glass
authors.forename: June
authors.initials: J
authors.lastname: Chan
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Frys
authors.forename: Martin
authors.initials: M
authors.lastname: Oselkin
authors.forename: M Jacqueline
authors.initials: MJ
authors.lastname: Tarsitano
authors.forename: Costantino
authors.initials: C
authors.lastname: Iadecola
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Pickel
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003712:Dendrites / Q000201:enzymology*; D006973:Hypertension / Q000139:chemically induced*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D017552:Solitary Nucleus / Q000166:cytology / Q000201:enzymology*; D013347:Subcellular Fractions / Q000201:enzymology* / Q000648:ultrastructure; D013566:Sympathomimetics / Q000494:pharmacology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D013566:Sympathomimetics; D000804:Angiotensin II; D010656:Phenylephrine; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1