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

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. Prospective, comparative, experimental study. Lambs, from birth until 8 weeks of age. 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. 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). 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.