Alterations in cGMP, soluble guanylate cyclase, phosphodiesterase 5, and B-type natriuretic peptide induced by chronic increased pulmonary blood flow in lambs.

Oishi, P; Sharma, S; Grobe, A; Azakie, A; Harmon, C; Johengen, MJ; Hsu, JH; Fratz, S; Black, SM; Fineman, JR

doi:10.1002/ppul.20696

2007

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Title:: Alterations in cGMP, soluble guanylate cyclase, phosphodiesterase 5, and B-type natriuretic peptide induced by chronic increased pulmonary blood flow in lambs.
Document type:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Author(s):: Oishi, P; Sharma, S; Grobe, A; Azakie, A; Harmon, C; Johengen, MJ; Hsu, JH; Fratz, S; Black, SM; Fineman, JR
Abstract:: OBJECTIVE: The objective of the study was to determine alterations in cGMP, soluble guanylate cyclase (sGC), phosphodiesterase type 5 (PDE5), and B-type natriuretic peptide (BNP), in an animal model of a congenital cardiac defect with increased pulmonary blood flow. DESIGN: Prospective, comparative, experimental study. SUBJECTS: Lambs, from birth until 8 weeks of age. METHODOLOGY: Late gestation fetal lambs underwent in utero placement of an 8 mm aortopulmonary vascular graft (shunt). In shunted and normal age-matched control lambs, at 2, 4, and 8 weeks of age, cGMP and BNP levels were measured, and sGC subunit and PDE5 protein expression were determined by Western blot analysis and immunohistochemistry. RESULTS: In shunted lambs, tissue and plasma cGMP levels were greater than normal throughout the 8-week study period (P < 0.05). sGCalpha protein was greater at 2 and 4 weeks (P < 0.05), and sGCbeta and PDE5 protein were greater at 4 weeks in shunted lambs (P < 0.05). Plasma BNP levels did not change in normal lambs but increased in shunted lambs by 8 weeks of age (P < 0.05). BNP levels were greater in shunted lambs than normal at 4 and 8 weeks (P < 0.05). CONCLUSIONS: Alterations in sGC subunit protein expression during the first post-natal month, and increased BNP levels during the second post-natal month contribute to elevations in plasma and lung tissue cGMP in lambs with increased pulmonary blood flow.
Journal title abbreviation:: Pediatr Pulmonol
Year:: 2007
Journal volume:: 42
Journal issue:: 11
Pages contribution:: 1057-71
Language:: eng
Fulltext / DOI:: doi:10.1002/ppul.20696
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/17902145
Print-ISSN:: 8755-6863
TUM Institution:: Klinik für Kinderkardiologie und angeborene Herzfehler (Prof. Hess)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Kinderkardiologie und angeborene Herzfehler (DHM) (Prof. Ewert)2007