sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension

Stephen M. Black, Lucienne S. Sanchez, Eugenia Mata-Greenwood, Janine M. Bekker, Robin H Steinhorn, Jeffrey R. Fineman

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Utilizing aortopulmonary vascular graft placement, we established a lamb model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. We previously demonstrated that endothelial nitric oxide synthase (eNOS) is increased in lambs at age 4 wk. However, these lambs display a selective impairment of endothelium-dependent pulmonary vasodilation that is suggestive of a derangement downstream of NO release. Thus our objective was to characterize potential alterations in the expression and activity of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5) induced by increased pulmonary blood flow and pulmonary hypertension. Late-gestational fetal lambs (n = 10) underwent in utero placement of an aortopulmonary vascular graft (shunt). Western blotting analysis on lung tissue from 4-wk-old shunted lambs and age-matched controls showed that protein for both subunits of sGC was increased in shunted lamb lungs compared with age-matched controls. Similarly, cGMP levels were increased in shunted lamb lungs compared with age-matched controls. However, PDE5 expression and activity were also increased in shunted lambs. Thus although cGMP generation was increased, concomitant upregulation of PDE5 expression and activity may have (at least partially) limited and accounted for the impairment of endothelium-dependent pulmonary vasodilation in shunted lambs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number5 25-5
StatePublished - 2001
Externally publishedYes

Keywords

  • Circulation
  • Phosphodiesterase type 5
  • Soluble guanylate cyclase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

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    Black, S. M., Sanchez, L. S., Mata-Greenwood, E., Bekker, J. M., Steinhorn, R. H., & Fineman, J. R. (2001). sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension. American Journal of Physiology - Lung Cellular and Molecular Physiology, 281(5 25-5).