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Article ; Online: Gene Therapy of the Peripheral Nervous System: Celiac Ganglia.

Hammond, Bradley / Kreulen, David L

Methods in molecular biology (Clifton, N.J.)

2016 Volume 1382, Page(s) 275–283

Abstract: Gene therapy has played an integral role in advancing our understanding of the central nervous system. However, gene therapy techniques have yet to be widely utilized in the peripheral nervous system. Critical targets for gene therapy within the PNS are ... ...

Abstract	Gene therapy has played an integral role in advancing our understanding of the central nervous system. However, gene therapy techniques have yet to be widely utilized in the peripheral nervous system. Critical targets for gene therapy within the PNS are the neurons in sympathetic ganglia, which are the final pathway to end organs. Thus they are the most specific targets for organ-specific neuron modification. This presents challenges because neurons are not viscerotopically organized within the ganglia and therefore cannot be targeted by their location. However, organ-specific neurons have been identified in sympathetic ganglia of some species and this offers an opportunity for targeting and transducing neurons by way of their target. In fact, alterations in sympathetic neurons have had pathological effects, and transducing organ-specific sympathetic neurons offer an exciting opportunity to selectively modify sympathetic pathology. In this chapter, we describe a method to virally transduce the celiac ganglion (CG), a prevertebral sympathetic ganglion that innervates abdominal organs, with AAV serotypes 1 and 6; thereby, providing a potential avenue to modulate specific subsets of neurons within the celiac ganglion.
MeSH term(s)	Animals ; Dependovirus/genetics ; Ganglia, Sympathetic/pathology ; Ganglia, Sympathetic/virology ; Genetic Therapy ; Genetic Vectors/administration & dosage ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Injections ; Male ; Rats ; Transduction, Genetic
Chemical Substances	Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-3271-9_20
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Article: Properties of the venous and arterial innervation in the mesentery.

Kreulen, David L

Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi

2004 Volume 39, Issue 6, Page(s) 269–279

MeSH term(s)	Animals ; Blood Pressure/physiology ; Humans ; Hypertension/metabolism ; Mesenteric Arteries/innervation ; Mesenteric Veins/innervation ; Nervous System Physiological Phenomena ; Neuroeffector Junction/metabolism ; Neurons, Afferent/physiology ; Neurotransmitter Agents/metabolism ; Norepinephrine Plasma Membrane Transport Proteins ; Reflex/physiology ; Sympathetic Nervous System/physiology ; Symporters/metabolism
Chemical Substances	Neurotransmitter Agents ; Norepinephrine Plasma Membrane Transport Proteins ; SLC6A2 protein, human ; Symporters
Language	English
Publishing date	2004-03-23
Publishing country	Japan
Document type	Journal Article ; Review
ISSN	0916-8737
ISSN	0916-8737
DOI	10.1540/jsmr.39.269
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Article ; Online: Soft Tissue Sarcoma of the Extremities: What Is the Value of Treating at High-volume Centers?

Lazarides, Alexander L / Kerr, David L / Nussbaum, Daniel P / Kreulen, R Timothy / Somarelli, Jason A / Blazer, Dan G / Brigman, Brian E / Eward, William C

Clinical orthopaedics and related research

2018 Volume 477, Issue 4, Page(s) 718–727

Abstract: Background: For many cancer types, survival is improved when patients receive management at treatment centers that encounter high numbers of patients annually. This correlation may be more important with less common malignancies such as sarcoma. ... ...

Abstract	Background: For many cancer types, survival is improved when patients receive management at treatment centers that encounter high numbers of patients annually. This correlation may be more important with less common malignancies such as sarcoma. Existing evidence, however, is limited and inconclusive as to whether facility volume may be associated with survival in soft tissue sarcoma. Questions/purposes: The purpose of this study was to examine the association between facility volume and overall survival in patients with soft tissue sarcoma of the extremities. In investigating this aim, we sought to (1) examine differences in the treatment characteristics of high- and low-volume facilities; (2) estimate the 5-year survival by facility volume; and (3) examine the association between facility volume and of traveling a further distance to a high-volume center and overall survival when controlling for confounding factors. Methods: The largest sarcoma patient registry to date is contained within the National Cancer Database (NCDB) and captures > 70% of new cancer diagnoses annually. We retrospectively analyzed 25,406 patients with soft tissue sarcoma of the extremities in the NCDB from 1998 through 2012. Patients were stratified based on per-year facility sarcoma volume and we used univariate comparisons and multivariate proportional hazards analyses to correlate survival measures with facility volume and various other patient-, tumor-, and treatment-related factors. First, we evaluated long-term survival for all variables using the Kaplan-Meier method with statistical comparisons based on the log-rank test. Multiple patient, tumor, and treatment characteristics were compared between the two facility-volume groups and then included them in the multivariate proportional hazards model. Of the 25,406 patients analyzed, 3310 were treated at high-volume centers (≥ 20 patients annually) and 22,096 were treated at low-volume centers. Patient demographics were generally not different between both patient cohorts, although patients treated at high-volume centers were more likely to have larger and higher grade tumors (64% versus 56% size ≥ 5 cm, 28% versus 14% undifferentiated grade, p < 0.001). Results: When controlling for patient, tumor, and treatment characteristics in a multivariate proportional hazards analysis, patients treated at high-volume facilities had an overall lower risk of mortality than those treated at low-volume centers (hazard ratio, 0.81 [0.75-0.88], p < 0.001). Patients treated at high-volume centers were also less likely to have positive margins (odds ratio [OR], 0.59 [0.52-0.68], p < 0.001) and in patients who received radiation, those treated at high-volume centers were more likely to have radiation before surgery (40.5% versus 21.7%, p < 0.001); there was no difference in the type of surgery performed (resection versus amputation) (OR, 1.01 [0.84-1.23], p = 0.883). Conclusions: With the largest patient cohort to date, this database review suggests that certain patients with soft tissue sarcoma of the extremities, particularly those with large high-grade tumors, may benefit from treatment at high-volume centers. Further investigation is necessary to help improve the referral of appropriate patients to high-volume sarcoma centers and to increase the treatment capacity of and access to such centers. Level of evidence: Level III, therapeutic study.
MeSH term(s)	Female ; Health Services Accessibility ; Hospitals, High-Volume ; Hospitals, Low-Volume ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Referral and Consultation ; Registries ; Retrospective Studies ; Risk Factors ; Sarcoma/mortality ; Sarcoma/pathology ; Sarcoma/surgery ; Soft Tissue Neoplasms/mortality ; Soft Tissue Neoplasms/pathology ; Soft Tissue Neoplasms/surgery ; Time Factors ; Transportation of Patients ; Treatment Outcome ; Tumor Burden ; United States
Language	English
Publishing date	2018-11-28
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	80301-7
ISSN	1528-1132 ; 0009-921X
ISSN (online)	1528-1132
ISSN	0009-921X
DOI	10.1097/01.blo.0000533623.60399.1b
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Article ; Online: Role of cardiac sympathetic nerves in blood pressure regulation.

Wehrwein, Erica A / Yoshimoto, Misa / Guzman, Pilar / Shah, Amit / Kreulen, David L / Osborn, John W

Autonomic neuroscience : basic & clinical

2014 Volume 183, Page(s) 30–35

Abstract: Stellate ganglionectomy (SGx) was used to assess the contribution of cardiac sympathetic nerves to neurogenic hypertension in deoxycorticosterone (DOCA)-salt treated rats. Experiments were conducted in two substrains of Sprague-Dawley (SD) rats since ... ...

Abstract	Stellate ganglionectomy (SGx) was used to assess the contribution of cardiac sympathetic nerves to neurogenic hypertension in deoxycorticosterone (DOCA)-salt treated rats. Experiments were conducted in two substrains of Sprague-Dawley (SD) rats since previous studies reported bradycardia in Charles River-SD (CR-SD) rats and tachycardia in SASCO-SD (SA-SD) rats with DOCA treatment suggesting different underlying neural mechanisms. Uninephrectomized male rats underwent SGx or SHAM surgery and were instrumented for telemetric monitoring of mean arterial pressure (MAP) and heart rate (HR). After recovery, 0.9% saline solution and DOCA (50mg) were administered. Baseline MAP (Days 0-5 average) after SGx in CR-SD rats (96±2mmHg; n=7) was not significantly different (p=0.08) than CR-SD SHAM rats (103±3mmHg; n=9); however, there was a significantly lower HR during the baseline period (377±7 vs. 432±7bpm, p<0.05) in SGx rats. In SA-SD rats baseline MAP was not different between SGx and SHAM rats and HR was lower in SGx rats (428±8 vs. 371±5bpm, p<0.05). After DOCA treatment in both substrains, MAP and HR were elevated similarly in SHAM and SGx groups showing minimal impact in both groups of SGx on hypertension development. However, overall MAP in SA-SD SHAM rats reached a significantly higher level (155±10mmHg vs 135±5mmHg, p<0.05) than that observed in CR-SD SHAM rats demonstrating that the magnitude of hypertensive response to DOCA-salt treatment varies between substrains. In conclusion, removal of cardiac sympathetic nerves did not alter the development or maintenance of DOCA-salt hypertension in SD rats.
MeSH term(s)	Animals ; Blood Pressure/physiology ; Desoxycorticosterone ; Disease Models, Animal ; Ganglionectomy ; Heart/physiopathology ; Heart Rate/physiology ; Hypertension/physiopathology ; Male ; Norepinephrine/metabolism ; Rats, Sprague-Dawley ; Species Specificity ; Stellate Ganglion/physiopathology ; Telemetry
Chemical Substances	Desoxycorticosterone (40GP35YQ49) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2014-03-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2014.02.005
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Article: Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase.

Dai, Xiaoling / Cao, Xian / Kreulen, David L

American journal of physiology. Heart and circulatory physiology

2005 Volume 290, Issue 3, Page(s) H1019–26

Abstract: Superoxide anion (O2-*) production is elevated in sympathetic ganglion neurons and in the vasculature of hypertensive animals; however, it is not known what enzymatic pathway(s) are responsible for O2-* production. To determine the pathway(s) of O2-* ... ...

Abstract	Superoxide anion (O2-) production is elevated in sympathetic ganglion neurons and in the vasculature of hypertensive animals; however, it is not known what enzymatic pathway(s) are responsible for O2- production. To determine the pathway(s) of O2-* production in sympathetic neurons, we examined the presence of mRNA of NADPH oxidase subunits in sympathetic ganglionic neurons and differentiated PC-12 cells. The mRNAs for NADPH oxidase subunits p47phox, p22phox, gp91phox, and NOX1 were present in sympathetic neurons and PC-12 cells, whereas the NOX4 homologue was present in sympathetic neurons but not PC-12 cells. Freshly dissociated celiac ganglion neurons from normal rats and PC-12 cells produced O2-* when treated with the PKC activator PMA; O2-* production increased by 317% and 254%, respectively. The PMA-evoked increases were reduced by pretreatment with the NADPH oxidase inhibitor apocynin. These findings indicate that NADPH oxidase is the primary source of O2-* in sympathetic ganglion neurons. When celiac ganglia from hypertensive rats were incubated with apocynin, O2-* levels were reduced to the same levels as normotensive animals, indicating that NADPH oxidase activity accounted for the elevated O2-* levels in hypertensive animals. To test this latter finding, we compared NADPH oxidase activity in extracts of prevertebral sympathetic ganglia of DOCA-salt hypertensive rats and sham-operated rats. NADPH oxidase activities were 49.9% and 78.6% higher in sympathetic ganglia of DOCA rats compared with normotensive controls when using beta-NADH and beta-NADPH as substrates, respectively. Thus elevated O2-* levels in hypertension may be a result of the increased activity of NADPH oxidase in postganglionic sympathetic neurons.
MeSH term(s)	Animals ; Desoxycorticosterone ; Enzyme Activation ; Ganglia, Sympathetic/metabolism ; Hypertension/chemically induced ; Hypertension/metabolism ; Male ; NADPH Oxidases/metabolism ; Neurons/metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxides/metabolism
Chemical Substances	Superoxides (11062-77-4) ; Desoxycorticosterone (40GP35YQ49) ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2005-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00052.2005
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Article ; Online: E-Cadherin Represses Anchorage-Independent Growth in Sarcomas through Both Signaling and Mechanical Mechanisms.

Molecular cancer research : MCR

2019 Volume 17, Issue 6, Page(s) 1391–1402

Abstract: CDH1 (also known as E-cadherin), an epithelial-specific cell-cell adhesion molecule, plays multiple roles in maintaining adherens junctions, regulating migration and invasion, and mediating intracellular signaling. Downregulation of E-cadherin is a ... ...

Abstract	CDH1 (also known as E-cadherin), an epithelial-specific cell-cell adhesion molecule, plays multiple roles in maintaining adherens junctions, regulating migration and invasion, and mediating intracellular signaling. Downregulation of E-cadherin is a hallmark of epithelial-to-mesenchymal transition (EMT) and correlates with poor prognosis in multiple carcinomas. Conversely, upregulation of E-cadherin is prognostic for improved survival in sarcomas. Yet, despite the prognostic benefit of E-cadherin expression in sarcoma, the mechanistic significance of E-cadherin in sarcomas remains poorly understood. Here, by combining mathematical models with wet-bench experiments, we identify the core regulatory networks mediated by E-cadherin in sarcomas, and decipher their functional consequences. Unlike carcinomas, E-cadherin overexpression in sarcomas does not induce a mesenchymal-to-epithelial transition (MET). However, E-cadherin acts to reduce both anchorage-independent growth and spheroid formation of sarcoma cells. Ectopic E-cadherin expression acts to downregulate phosphorylated CREB1 (p-CREB) and the transcription factor, TBX2, to inhibit anchorage-independent growth. RNAi-mediated knockdown of TBX2 phenocopies the effect of E-cadherin on CREB levels and restores sensitivity to anchorage-independent growth in sarcoma cells. Beyond its signaling role, E-cadherin expression in sarcoma cells can also strengthen cell-cell adhesion and restricts spheroid growth through mechanical action. Together, our results demonstrate that E-cadherin inhibits sarcoma aggressiveness by preventing anchorage-independent growth. IMPLICATIONS: We highlight how E-cadherin can restrict aggressive behavior in sarcomas through both biochemical signaling and biomechanical effects.
MeSH term(s)	Antigens, CD/metabolism ; Cadherins/metabolism ; Cell Line, Tumor ; Cell Proliferation/physiology ; Down-Regulation/physiology ; Epithelial-Mesenchymal Transition/physiology ; Humans ; Prognosis ; Sarcoma/metabolism ; Signal Transduction/physiology ; Up-Regulation/physiology
Chemical Substances	Antigens, CD ; CDH1 protein, human ; Cadherins
Language	English
Publishing date	2019-03-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-18-0763
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Article ; Online: Differential regulation of NADPH oxidase in sympathetic and sensory Ganglia in deoxycorticosterone acetate salt hypertension.

Cao, Xian / Dai, Xiaoling / Parker, Lindsay M / Kreulen, David L

Hypertension (Dallas, Tex. : 1979)

2007 Volume 50, Issue 4, Page(s) 663–671

Abstract: We demonstrated recently that superoxide anion levels are elevated in prevertebral sympathetic ganglia of deoxycorticosterone acetate-salt hypertensive rats and that this superoxide anion is generated by reduced nicotinamide-adenine dinucleotide ... ...

Abstract	We demonstrated recently that superoxide anion levels are elevated in prevertebral sympathetic ganglia of deoxycorticosterone acetate-salt hypertensive rats and that this superoxide anion is generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase. In this study we compared the reduced nicotinamide-adenine dinucleotide phosphate oxidase enzyme system of dorsal root ganglion (DRG) and sympathetic celiac ganglion (CG) and its regulation in hypertension. The reduced nicotinamide-adenine dinucleotide phosphate oxidase activity of ganglion extracts was measured using fluorescence spectrometry of dihydroethidine; the activity in hypertensive dorsal root ganglion was 34% lower than in normotensive DRG. In contrast, activity was 79% higher in hypertensive CG than normotensive CG. mRNA for the oxidase subunits NOX1, NOX2, NOX4, p47(phox), and p22(phox) were present in both CG and DRG; mRNA for NOX4 was significantly higher in CG than in DRG. The levels of mRNA and protein expression of the membrane-bound catalytic subunit p22(phox) and of the regulatory subunits p47(phox) and Rac-1 were measured in CG and DRG in normotensive and hypertensive rats. p22(phox) mRNA and protein expression was greater in CG of hypertensive rats but not in DRG. Compared with normotensive controls, p47(phox) mRNA and protein, as well as Rac-1 protein, were significantly decreased in hypertensive DRG but not in CG. Immunohistochemical staining of p47(phox) showed translocation from cytoplasm to membrane in hypertensive CG but not in hypertensive DRG. This suggests that reduced nicotinamide-adenine dinucleotide phosphate oxidase activation in sympathetic neurons and sensory neurons is regulated in opposite directions in hypertension. This differential regulation may contribute to unbalanced vasomotor control and enhanced vasoconstriction in the splanchnic circulation.
MeSH term(s)	Animals ; Blood Pressure/physiology ; Desoxycorticosterone ; Ganglia, Sensory/enzymology ; Ganglia, Sensory/physiology ; Ganglia, Sympathetic/enzymology ; Ganglia, Sympathetic/physiology ; Gene Expression Regulation, Enzymologic ; Hypertension/chemically induced ; Hypertension/enzymology ; Hypertension/physiopathology ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; Neurons, Afferent/metabolism ; Oxidative Stress/physiology ; Oxygen/metabolism ; Protein Subunits/genetics ; Protein Subunits/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rats ; Rats, Inbred Dahl ; Superoxides/metabolism
Chemical Substances	Protein Subunits ; RNA, Messenger ; Superoxides (11062-77-4) ; Desoxycorticosterone (40GP35YQ49) ; NADPH Oxidases (EC 1.6.3.-) ; Cyba protein, rat (EC 1.6.3.1) ; neutrophil cytosolic factor 1 (EC 1.6.3.1) ; Oxygen (S88TT14065)
Language	English
Publishing date	2007-08-13
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.107.089748
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Article ; Online: Regional changes in cardiac and stellate ganglion norepinephrine transporter in DOCA-salt hypertension.

Wehrwein, Erica A / Novotny, Martin / Swain, Greg M / Parker, Lindsay M / Esfahanian, Mohammad / Spitsbergen, John M / Habecker, Beth A / Kreulen, David L

Autonomic neuroscience : basic & clinical

2013 Volume 179, Issue 1-2, Page(s) 99–107

Abstract: Uptake of norepinephrine via the neuronal norepinephrine transporter is reduced in the heart during deoxycorticosterone (DOCA)-salt hypertension. We hypothesized that this was due to reduced norepinephrine transporter mRNA and/or protein expression in ... ...

Abstract	Uptake of norepinephrine via the neuronal norepinephrine transporter is reduced in the heart during deoxycorticosterone (DOCA)-salt hypertension. We hypothesized that this was due to reduced norepinephrine transporter mRNA and/or protein expression in the stellate ganglia and heart. After 4 weeks of DOCA-salt treatment there was no change in norepinephrine transporter mRNA in either the right or the left stellate ganglia from hypertensive rats (n=5-7, p>0.05). Norepinephrine transporter immunoreactivity in the left stellate ganglion was significantly increased (n=4, p<0.05) while the right stellate ganglion was unchanged (n=4, p>0.05). Whole heart norepinephrine content was significantly reduced in DOCA rats consistent with reduced uptake function; however, when norepinephrine was assessed by chamber, a significant decrease was noted only in the right atrium and right ventricle (n=6, p<0.05). Cardiac norepinephrine transport binding by chamber revealed that it was only reduced in the left atrium (n=5-7, p>0.05). Therefore, 1) contrary to our hypothesis reduced reuptake in the hypertensive heart is not exclusively due to an overall reduction in norepinephrine transporter mRNA or protein in the stellate ganglion or heart, and 2) norepinephrine transporter regulation occurs regionally in the heart and stellate ganglion in the hypertensive rat heart.
MeSH term(s)	Animals ; Desoxycorticosterone Acetate/toxicity ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Heart/physiology ; Hypertension/chemically induced ; Hypertension/metabolism ; Immunohistochemistry ; Male ; Mineralocorticoids/toxicity ; Myocardium/metabolism ; Norepinephrine Plasma Membrane Transport Proteins/biosynthesis ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Sodium Chloride, Dietary/toxicity ; Stellate Ganglion/metabolism
Chemical Substances	Mineralocorticoids ; Norepinephrine Plasma Membrane Transport Proteins ; Sodium Chloride, Dietary ; Desoxycorticosterone Acetate (6E0A168OB8)
Language	English
Publishing date	2013-08-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2013.08.070
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Article ; Online: Localization of NADPH oxidase in sympathetic and sensory ganglion neurons and perivascular nerve fibers.

Cao, Xian / Demel, Stacie L / Quinn, Mark T / Galligan, James J / Kreulen, David

Autonomic neuroscience : basic & clinical

2009 Volume 151, Issue 2, Page(s) 90–97

Abstract: Superoxide anion (O(2)(-*)) production was previously reported to be increased in celiac ganglia (CG) during DOCA-salt hypertension, possibly via activation of the reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase. This suggested a role ...

Abstract	Superoxide anion (O(2)(-)) production was previously reported to be increased in celiac ganglia (CG) during DOCA-salt hypertension, possibly via activation of the reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase. This suggested a role for neuronal NADPH oxidase in autonomic neurovascular control. However, the expression and localization of NADPH oxidase in the peripheral neurons are not fully known. The purpose of this study was to examine the subcellular localization of NADPH oxidase in sympathetic and sensory ganglion neurons and perivascular nerve fibers. In rat CG, p22(phox) and neuropeptide Y (NPY) were colocalized in all neurons. P22(phox) was also localized to dorsal root ganglia (DRG) neurons that contain calcitonin gene related peptide (CGRP). In mesenteric arteries, p22(phox) and p47(phox) were colocalized with NPY or CGRP in perivascular nerve terminals. A similar pattern of nerve terminal staining of p22(phox) and p47(phox) was also found in cultured CG neurons and nerve growth factor (NGF)-differentiated PC12 cells. These data demonstrate a previously uncharacterized localization of NADPH oxidase in perivascular nerve fibers. The presence of a O(2)(-)-generating enzyme in close vicinity to the sites of neurotransmitter handling in the nerve fibers suggests the possibility of novel redox-mediated mechanisms in peripheral neurovascular control.
MeSH term(s)	Animals ; Animals, Newborn ; Blood Vessels/innervation ; Blood Vessels/physiology ; Calcitonin Gene-Related Peptide/metabolism ; Ganglia, Sensory/cytology ; Ganglia, Sensory/enzymology ; Ganglia, Spinal/cytology ; Ganglia, Spinal/enzymology ; Ganglia, Sympathetic/cytology ; Ganglia, Sympathetic/enzymology ; NADH, NADPH Oxidoreductases/metabolism ; NADPH Oxidase 1 ; NADPH Oxidases/metabolism ; Nerve Fibers, Myelinated/enzymology ; Nerve Fibers, Myelinated/ultrastructure ; Neurons/cytology ; Neurons/enzymology ; Neuropeptide Y/metabolism ; Oxidation-Reduction ; PC12 Cells ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Regional Blood Flow/physiology ; Sensory Receptor Cells/cytology ; Sensory Receptor Cells/enzymology ; Superoxides/metabolism ; Sympathetic Fibers, Postganglionic/cytology ; Sympathetic Fibers, Postganglionic/enzymology ; Vasoconstriction/physiology ; Vasodilation/physiology
Chemical Substances	Neuropeptide Y ; Superoxides (11062-77-4) ; NADH, NADPH Oxidoreductases (EC 1.6.-) ; NADPH Oxidase 1 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-) ; Cyba protein, rat (EC 1.6.3.1) ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
Language	English
Publishing date	2009-08-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2009.07.010
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Article: Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo.

Lau, Yanny E / Galligan, James J / Kreulen, David L / Fink, Gregory D

American journal of physiology. Regulatory, integrative and comparative physiology

2005 Volume 290, Issue 1, Page(s) R90–5

Abstract: Dai and colleagues (Dai X, Galligan JJ, Watts SW, Fink GD, and Kreulen DL. Hypertension 43: 1048 ...

Abstract	Dai and colleagues (Dai X, Galligan JJ, Watts SW, Fink GD, and Kreulen DL. Hypertension 43: 1048-1054, 2004) found that endothelin (ET) stimulated O2- production in sympathetic ganglion neurons in vitro by activating ET(B) receptors. The objective of the present study was to determine whether activation of ET(B) receptors in vivo elevates O2- levels in sympathetic ganglia. Because ET(B) receptor activation increases blood pressure, we also sought to determine whether alteration in O2- levels was a direct effect of ET(B) receptor activation on sympathetic ganglia or an indirect consequence of hypertension. Male Sprague-Dawley rats received intravenous infusions of either the specific ET(B) receptor agonist sarafotoxin 6c (S6c; 5 pmol.kg(-1).min(-1)) or isotonic saline at 0.01 ml/min (control) for 120 min. To measure O2- levels, we removed the inferior mesenteric ganglion immediately after infusion and stained it with dihydroethidine (DHE). Mean arterial pressure increased 26.6 +/- 1.7 mmHg in the S6c-treated rats and 3.65 +/- 6 mmHg in control rats. Measurements of average pixel intensity revealed that the DHE fluorescence in ganglionic neurons and surrounding glial cells were 96.7% and 160% greater in S6c-treated than in control rats, respectively. To evaluate the effect of elevated blood pressure on O2- production, a separate group of rats received phenylephrine (PE; 10 mug.kg(-1).min(-1) iv) for 2 h. MAP increased 31 +/- 1.2 mmHg in PE-infused rats. The DHE fluorescence intensity in ganglia of PE-infused rats was significantly greater than that of control rats, 137.7% in neurons and 104.6% in glia but significantly lower than in ganglia from S6c rats. We conclude that ET(B) receptor activation in vivo significantly enhances O2- levels in sympathetic ganglia, due to both pressor effects and direct stimulation of ET(B) receptors in ganglion cells.
MeSH term(s)	Animals ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Endothelin-1/metabolism ; Ganglia, Sympathetic/metabolism ; Male ; Phenylephrine ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin A/metabolism ; Receptor, Endothelin B/metabolism ; Superoxides/metabolism ; Viper Venoms
Chemical Substances	Endothelin-1 ; Receptor, Endothelin A ; Receptor, Endothelin B ; Viper Venoms ; sarafotoxins s6 ; Superoxides (11062-77-4) ; Phenylephrine (1WS297W6MV)
Language	English
Publishing date	2005-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00505.2005
Database	MEDical Literature Analysis and Retrieval System OnLINE

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