| Neurotrophins induce nitric oxide generation in human pulmonary artery endothelial cells. | |
| | |
MedLine Citation:
|
PMID: 21498417 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
AIMS: Members of the growth factor family of neurotrophins [NTs; e.g. brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3)] and their high-affinity receptors (tropomyosin-related kinase; Trk) and low-affinity receptors p75 neurotrophin receptor (p75NTR) have been localized to pulmonary artery (PA) in humans. However, their role is unclear. Based on previous findings of NTs and their receptors within the pulmonary endothelium, we tested the hypothesis that NTs induce nitric oxide (NO) production in pulmonary endothelial cells (ECs), thus contributing to vasodilation. METHODS AND RESULTS: In human pulmonary artery ECs loaded with the NO-sensitive fluorescent dye diaminofluorescein-2, both BDNF and NT3 (100 pM, 1 nM, and 10 nM) acutely (<10 min) and substantially increased fluorescence levels in a concentration-dependent fashion (to levels comparable to that induced by 1 μM acetylcholine). NT-induced elevation of NO levels was blunted by the tyrosine kinase inhibitor K252a, the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester, the Ca(2+) chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, and the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. Suppression of TrkB or TrkC expression via siRNA as well as functional blockade of p75NTR prevented NT-induced NO elevation. Both BDNF and NT3 increased phosphorylation of Akt and endothelial NO synthase (eNOS). In endothelium-intact porcine PA rings, NTs increased cGMP and induced vasodilation in pre-contracted arteries. CONCLUSION: These results indicate that NTs acutely modulate pulmonary endothelial NO production and contribute to relaxation of the pulmonary vasculature. |
| | |
Authors:
|
Lucas W Meuchel; Michael A Thompson; Steven D Cassivi; Christina M Pabelick; Y S Prakash |
Related Documents
:
|
11040857 - Calcified bicuspid aortic valve mass prolapsing into the left main coronary artery. 9663547 - Combined tracheal resection and aortic valve replacement with a cryopreserved aortic va... 1610597 - Technique of aortic valve replacement with the edwards stentless aortic bioprosthesis 2... 18772627 - Heart failure and "inoperable" aortic stenosis: staged balloon aortic valvuloplasty and... 20956167 - Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: path... 7042187 - Gas exchange in the adult respiratory distress syndrome. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-04-14 |
Journal Detail:
|
Title: Cardiovascular research Volume: 91 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2011 Sep |
Date Detail:
|
Created Date: 2011-08-17 Completed Date: 2011-12-30 Revised Date: 2012-04-26 |
Medline Journal Info:
|
Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
|
Languages: eng Pagination: 668-76 Citation Subset: IM |
Affiliation:
|
Department of Physiology, Mayo Clinic College of Medicine, 4-184 W. Jos SMH, Rochester, MN 55905, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylcholine
/
pharmacology Brain-Derived Neurotrophic Factor / pharmacology* Cells, Cultured Endothelial Cells / metabolism* Humans Neurotrophin 3 / pharmacology* Nitric Oxide / biosynthesis* Nitric Oxide Synthase Type III / metabolism Phosphorylation Proto-Oncogene Proteins c-akt / metabolism Pulmonary Artery / metabolism* RNA, Small Interfering / genetics Receptor, Nerve Growth Factor / physiology Receptor, trkB / physiology |
| Grant Support | |
ID/Acronym/Agency:
|
HL056470/HL/NHLBI NIH HHS; HL088029/HL/NHLBI NIH HHS; HL09595/HL/NHLBI NIH HHS; R01 HL088029/HL/NHLBI NIH HHS; R01 HL088029-04/HL/NHLBI NIH HHS; R01 HL090595-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Brain-Derived Neurotrophic Factor; 0/Neurotrophin 3; 0/RNA, Small Interfering; 0/Receptor, Nerve Growth Factor; 10102-43-9/Nitric Oxide; 51-84-3/Acetylcholine; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 2.7.10.1/Receptor, trkB; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Pharyngeal mesoderm development during embryogenesis: Implications for both heart and head myogenesi...
Next Document: Inhibition of MDM2 Attenuates Neointimal Hyperplasia via Suppression of Vascular Proliferation and I...