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

Pediatr Pulmonol. 2007 Nov;42(11):1057-71. doi: 10.1002/ppul.20696.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Animals, Suckling
  • Cyclic GMP / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
  • Disease Models, Animal
  • Gene Expression Profiling
  • Guanylate Cyclase / metabolism*
  • Heart Defects, Congenital / complications*
  • Heart Defects, Congenital / physiopathology*
  • Natriuretic Peptide, Brain / metabolism
  • Pulmonary Circulation / physiology*
  • Sheep


  • Natriuretic Peptide, Brain
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Guanylate Cyclase
  • Cyclic GMP