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

74 Citations (Scopus)

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)
Pages (from-to)L1051-L1057
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number5 25-5
StatePublished - Dec 17 2001

Fingerprint

Type 5 Cyclic Nucleotide Phosphodiesterases
Pulmonary Hypertension
Lung
Vasodilation
Endothelium
Blood Vessels
Transplants
Nitric Oxide Synthase Type III
Protein Subunits
Soluble Guanylyl Cyclase
Heart Diseases
Up-Regulation
Western Blotting

Keywords

  • Circulation
  • Phosphodiesterase type 5
  • Soluble guanylate cyclase

ASJC Scopus subject areas

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

Cite this

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), L1051-L1057.

sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension. / Black, Stephen M.; Sanchez, Lucienne S.; Mata-Greenwood, Eugenia; Bekker, Janine M.; Steinhorn, Robin H.; Fineman, Jeffrey R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 281, No. 5 25-5, 17.12.2001, p. L1051-L1057.

Research output: Contribution to journalArticle

Black, SM, Sanchez, LS, Mata-Greenwood, E, Bekker, JM, Steinhorn, RH & Fineman, JR 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, vol. 281, no. 5 25-5, pp. L1051-L1057.
Black SM, Sanchez LS, Mata-Greenwood E, Bekker JM, Steinhorn RH, Fineman JR. sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2001 Dec 17;281(5 25-5):L1051-L1057.
Black, Stephen M. ; Sanchez, Lucienne S. ; Mata-Greenwood, Eugenia ; Bekker, Janine M. ; Steinhorn, Robin H. ; Fineman, Jeffrey R. / sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2001 ; Vol. 281, No. 5 25-5. pp. L1051-L1057.
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