Increased endothelial NOS in lambs with increased pulmonary blood flow and pulmonary hypertension

Stephen M. Black, Jeffrey R. Fineman, Robin H. Steinhorn, James Bristow, Scott J. Soifer

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Altered pulmonary vascular reactivity is a source of morbidity and mortality for children with congenital heart defects and increased pulmonary blood flow. Nitric oxide (NO) is an important mediator of pulmonary vascular reactivity. The objective of this study was to characterize potential early alterations in expression, localization, and activity of endothelial NO synthase (eNOS) induced by increased pulmonary blood flow and pulmonary hypertension. Utilizing aortopulmonary vascular graft placement in the fetal lamb, we have established a unique animal model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. Ten fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt). RNase protection assays and Western blotting were performed on lung tissue prepared from 4-wk-old shunt lambs and age-matched controls. eNOS mRNA (2.4:1, P < 0.05) and protein (2.08:1, P < 0.05) were increased in lungs of shunt lambs. In situ hybridization and immunohistochemistry revealed that the increase was confined to the endothelium of pulmonary arteries. eNOS protein (1.55:1, P < 0.05) and tissue cGMP concentrations (2.1:1, P < 0.05) were also increased in isolated fifth-generation pulmonary arteries of shunt lambs. In addition, total lung eNOS activity was increased (2.9:1, P < 0.05). Thus we report a previously undescribed, early upregulation of eNOS gene expression and activity in lambs with increased pulmonary blood flow and pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)H1843-51
Number of pages9
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume275
Issue number5 Pt 2
StatePublished - Nov 1 1998

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Pulmonary Hypertension
Lung
Nitric Oxide Synthase
Blood Vessels
Pulmonary Artery
Transplants
Child Mortality
Congenital Heart Defects
Nitric Oxide Synthase Type III
Ribonucleases
Endothelium
In Situ Hybridization
Heart Diseases
Nitric Oxide
Proteins
Up-Regulation
Animal Models
Western Blotting
Immunohistochemistry
Morbidity

Keywords

  • Endothelial nitric oxide synthase
  • Nitric oxide
  • Pulmonary circulation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Black, S. M., Fineman, J. R., Steinhorn, R. H., Bristow, J., & Soifer, S. J. (1998). Increased endothelial NOS in lambs with increased pulmonary blood flow and pulmonary hypertension. American Journal of Physiology - Heart and Circulatory Physiology, 275(5 Pt 2), H1843-51.

Increased endothelial NOS in lambs with increased pulmonary blood flow and pulmonary hypertension. / Black, Stephen M.; Fineman, Jeffrey R.; Steinhorn, Robin H.; Bristow, James; Soifer, Scott J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 275, No. 5 Pt 2, 01.11.1998, p. H1843-51.

Research output: Contribution to journalArticle

Black, SM, Fineman, JR, Steinhorn, RH, Bristow, J & Soifer, SJ 1998, 'Increased endothelial NOS in lambs with increased pulmonary blood flow and pulmonary hypertension', American Journal of Physiology - Heart and Circulatory Physiology, vol. 275, no. 5 Pt 2, pp. H1843-51.
Black, Stephen M. ; Fineman, Jeffrey R. ; Steinhorn, Robin H. ; Bristow, James ; Soifer, Scott J. / Increased endothelial NOS in lambs with increased pulmonary blood flow and pulmonary hypertension. In: American Journal of Physiology - Heart and Circulatory Physiology. 1998 ; Vol. 275, No. 5 Pt 2. pp. H1843-51.
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