Heterogeneous distribution of soluble guanylate cyclase in the pulmonary vasculature of the fetal lamb

Christopher A. D'Angelis, Peter A. Nickerson, Robin H Steinhorn, Frederick C. Morin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Vascular segments in the fetal lung differ anatomically and functionally from one another. At birth, the nitric oxide (NO) pathway plays an integral role in reducing pulmonary vascular resistance through a marked vasodilation. However, the contributions of each vascular segment to this dilation are unclear. We sought to determine the distribution of soluble guanylate cyclase (sGC), the enzyme NO activates to induce vasodilation across the pulmonary vasculature. Methods: Pulmonary airspaces were expanded with freezing compound and the pulmonary arterial tree was infused with barium sulfate gelatin. Soluble guanylate cyclase was localized by immunohistochemistry across the pulmonary vasculature of four near-term fetal lambs and its immunoreaction product was assessed by a semiquantitative method. The physiologic response of fourth- and fifth-generation arteries and veins isolated from age-matched lambs to NO was measured using standard tissue bath techniques. Results: Clear differences in sGC immunostaining were present throughout the pulmonary vasculature: very weak to absent in large arteries accompanying bronchi, but intensely positive for veins. This pronounced staining for sGC in preacinar veins correlated with a 100-fold greater sensitivity to NO in veins compared to arteries of the same generation. The percentage of arteries staining positively approached 100% at the level of respiratory bronchioles and alveoli. Conclusions: These findings suggest that the increased response to NO in preacinar veins compared to that of arteries is in part due to increased sGC within venous vascular smooth muscle. Furthermore, intense staining within distal arteries implies a greater role for NO-mediated vasodilation within these segments.

Original languageEnglish (US)
Pages (from-to)62-69
Number of pages8
JournalAnatomical Record
Volume250
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Fingerprint

guanylate cyclase
nitric oxide
Nitric Oxide
lambs
arteries
Arteries
lungs
Veins
Lung
blood vessels
vasodilation
Vasodilation
Staining and Labeling
Blood Vessels
Barium Sulfate
Bronchioles
barium sulfate
dilation
barium
Bronchi

Keywords

  • Fetus
  • Guanylate cyclase
  • Lung
  • Nitric oxide
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Anatomy

Cite this

Heterogeneous distribution of soluble guanylate cyclase in the pulmonary vasculature of the fetal lamb. / D'Angelis, Christopher A.; Nickerson, Peter A.; Steinhorn, Robin H; Morin, Frederick C.

In: Anatomical Record, Vol. 250, No. 1, 01.1998, p. 62-69.

Research output: Contribution to journalArticle

D'Angelis, Christopher A. ; Nickerson, Peter A. ; Steinhorn, Robin H ; Morin, Frederick C. / Heterogeneous distribution of soluble guanylate cyclase in the pulmonary vasculature of the fetal lamb. In: Anatomical Record. 1998 ; Vol. 250, No. 1. pp. 62-69.
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AB - Background: Vascular segments in the fetal lung differ anatomically and functionally from one another. At birth, the nitric oxide (NO) pathway plays an integral role in reducing pulmonary vascular resistance through a marked vasodilation. However, the contributions of each vascular segment to this dilation are unclear. We sought to determine the distribution of soluble guanylate cyclase (sGC), the enzyme NO activates to induce vasodilation across the pulmonary vasculature. Methods: Pulmonary airspaces were expanded with freezing compound and the pulmonary arterial tree was infused with barium sulfate gelatin. Soluble guanylate cyclase was localized by immunohistochemistry across the pulmonary vasculature of four near-term fetal lambs and its immunoreaction product was assessed by a semiquantitative method. The physiologic response of fourth- and fifth-generation arteries and veins isolated from age-matched lambs to NO was measured using standard tissue bath techniques. Results: Clear differences in sGC immunostaining were present throughout the pulmonary vasculature: very weak to absent in large arteries accompanying bronchi, but intensely positive for veins. This pronounced staining for sGC in preacinar veins correlated with a 100-fold greater sensitivity to NO in veins compared to arteries of the same generation. The percentage of arteries staining positively approached 100% at the level of respiratory bronchioles and alveoli. Conclusions: These findings suggest that the increased response to NO in preacinar veins compared to that of arteries is in part due to increased sGC within venous vascular smooth muscle. Furthermore, intense staining within distal arteries implies a greater role for NO-mediated vasodilation within these segments.

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