Altered reactivity and nitric oxide signaling in the isolated thoracic duct from an ovine model of congenital heart disease with increased pulmonary blood flow
| Autor: | Sanjeev A. Datar, Michael J. Johengen, Jun Maki, Peter Oishi, Christine E. Sun, Stephen H. Bennett, Wenhui Gong, Jeffrey R. Fineman, Rebecca C. Johnson, Gary W. Raff |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Pulmonary Circulation
Time Factors Physiology Vascular Biology and Microcirculation Muscle Relaxation Medical Physiology Cardiovascular Congenital chemistry.chemical_compound Norepinephrine 2.1 Biological and endogenous factors Aetiology Lung Cyclic GMP Heart Defects Pediatric nitric oxide-cGMP signaling Muscle relaxation Lymphatic system medicine.anatomical_structure Inhalation Anesthesia Administration Cardiology Lymph Drug medicine.symptom Endothelium Lymphatic Lymphatic Cardiology and Cardiovascular Medicine Blood Flow Velocity Muscle Contraction Signal Transduction Heart Defects Congenital medicine.medical_specialty Pulmonary Artery S-Nitroso-N-Acetylpenicillamine Nitric Oxide Thoracic duct Nitric oxide Thoracic Duct Dose-Response Relationship Physiology (medical) medicine.artery Internal medicine Administration Inhalation medicine Animals Nitric Oxide Donors Endothelium Sheep Dose-Response Relationship Drug Animal business.industry Perinatal Period - Conditions Originating in Perinatal Period Disease Models Animal Cardiovascular System & Hematology chemistry lymphatic endothelial function Dilator Disease Models Pulmonary artery business Vasoconstriction |
| Zdroj: | American journal of physiology. Heart and circulatory physiology, vol 306, iss 7 Datar, SA; Oishi, PE; Gong, W; Bennett, SH; Sun, CE; Johengen, M; et al.(2014). Altered reactivity and nitric oxide signaling in the isolated thoracic duct from an ovine model of congenital heart disease with increased pulmonary blood flow. American Journal of Physiology-Heart and Circulatory Physiology, 306(7), H954-H962. doi: 10.1152/ajpheart.00841.2013. UCSF: Retrieved from: http://www.escholarship.org/uc/item/0pk8x82r |
| Popis: | We have previously shown decreased pulmonary lymph flow in our lamb model of chronically increased pulmonary blood flow, created by the in utero placement of an 8-mm aortopulmonary shunt. The purpose of this study was to test the hypothesis that abnormal lymphatic function in shunt lambs is due to impaired lymphatic endothelial nitric oxide (NO)-cGMP signaling resulting in increased lymphatic vascular constriction and/or impaired relaxation. Thoracic duct rings were isolated from 4-wk-old shunt ( n = 7) and normal ( n = 7) lambs to determine length-tension properties, vascular reactivity, and endothelial NO synthase protein. At baseline, shunt thoracic duct rings had 2.6-fold higher peak to peak tension and a 2-fold increase in the strength of contractions compared with normal rings ( P < 0.05). In response to norepinephrine, shunt thoracic duct rings had a 2.4-fold increase in vascular tone compared with normal rings ( P < 0.05) and impaired relaxation in response to the endothelium-dependent dilator acetylcholine (63% vs. 13%, P < 0.05). In vivo, inhaled NO (40 ppm) increased pulmonary lymph flow (normalized for resistance) ∼1.5-fold in both normal and shunt lambs ( P < 0.05). Inhaled NO exposure increased bioavailable NO [nitrite/nitrate (NO x); ∼2.5-fold in normal lambs and ∼3.4-fold in shunt lambs] and cGMP (∼2.5-fold in both) in the pulmonary lymph effluent ( P < 0.05). Chronic exposure to increased pulmonary blood flow is associated with pulmonary lymphatic endothelial injury that disrupts NO-cGMP signaling, leading to increased resting vasoconstriction, increased maximal strength of contraction, and impaired endothelium-dependent relaxation. Inhaled NO increases pulmonary lymph NO x and cGMP levels and pulmonary lymph flow in normal and shunt lambs. Therapies that augment NO-cGMP signaling within the lymphatic system may provide benefits, warranting further study. |
| Databáze: | OpenAIRE |
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