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Alterations in cGMP, soluble guanylate cyclase, phosphodiesterase 5, and B‐type natriuretic peptide induced by chronic increased pulmonary blood flow in lambs
Author(s) -
Oishi Peter,
Sharma Shruti,
Grobe Albert,
Azakie Anthony,
Harmon Cynthia,
Johengen Michael J.,
Hsu JongHau,
Fratz Sohrab,
Black Stephen M.,
Fineman Jeffrey R.
Publication year - 2007
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.20696
Subject(s) - medicine , natriuretic peptide , endocrinology , cgmp specific phosphodiesterase type 5 , brain natriuretic peptide , phosphodiesterase , in utero , pulmonary hypertension , lung , fetus , sildenafil , heart failure , biology , pregnancy , enzyme , biochemistry , genetics
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). sGCα protein was greater at 2 and 4 weeks ( P < 0.05), and sGCβ 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. 2007;42:1057–1071. © 2007 Wiley‐Liss, Inc.