Increased lung endothelin-1 production in rats with idiopathic pulmonary hypertension

T. J. Stelzner, R. F. O'Brien, M. Yanagisawa, T. Sakurai, K. Sato, S. Webb, M. Zamora, I. F. McMurtry, J. H. Fisher

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

The role of endogenous circulating or locally produced endothelin-1 (ET-1) in pulmonary hypertensive states is unknown. To investigate this we measured ET-1 levels and preproendothelin-1 (preproET-1) mRNA expression at various ages in control Sprague-Dawley (SDR) rats and in fawn-hooded rats (FHR), a strain which develops idiopathic pulmonary hypertension. Although serum ET-1 levels were similar in SDR and FHR, we found twofold increases in FHR whole lung homogenate ET-1 levels by radioimmunoassay. Coexisting threefold increases in preproET-1 mRNA expression were found in FHR lungs by densitometric analysis of Northern blots and by filter hybridization, suggesting the increase in lung ET-1 was due to enhanced intrapulmonary production of the peptide. To test whether the increase in lung preproET-1 mRNA was primary or secondary to established pulmonary hypertension, we compared preproET-1 mRNA expression prior to development of pulmonary hypertension in fetal (19 day gestation) and neonatal (5 day old) FHR and SDR. Despite similar right ventricular size in SDR and FHR, preproET-1 mRNA was already elevated in neonatal FHR lungs. Furthermore, we found no increase in lung preproET-1 mRNA or ET-1 levels in adult SDR with an equivalent degree of pulmonary hypertension due to chronic hypoxia, implying that the increases in ET-1 production in FHR were not a common consequence of all pulmonary hypertensive states. The functional significance of these observations remains unclear but raises the possibility of a role for ET-1 in the pathophysiology of pulmonary hypertension in the FHR.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume262
Issue number5 6-5
StatePublished - 1992

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Endothelin-1
Lung
Pulmonary Hypertension
Messenger RNA
Familial Primary Pulmonary Hypertension
Northern Blotting
Radioimmunoassay
Sprague Dawley Rats

Keywords

  • fawn-hooded rat
  • hypoxic pulmonary hypertension
  • transcriptional control

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

Increased lung endothelin-1 production in rats with idiopathic pulmonary hypertension. / Stelzner, T. J.; O'Brien, R. F.; Yanagisawa, M.; Sakurai, T.; Sato, K.; Webb, S.; Zamora, M.; McMurtry, I. F.; Fisher, J. H.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 262, No. 5 6-5, 1992.

Research output: Contribution to journalArticle

Stelzner, TJ, O'Brien, RF, Yanagisawa, M, Sakurai, T, Sato, K, Webb, S, Zamora, M, McMurtry, IF & Fisher, JH 1992, 'Increased lung endothelin-1 production in rats with idiopathic pulmonary hypertension', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 262, no. 5 6-5.
Stelzner, T. J. ; O'Brien, R. F. ; Yanagisawa, M. ; Sakurai, T. ; Sato, K. ; Webb, S. ; Zamora, M. ; McMurtry, I. F. ; Fisher, J. H. / Increased lung endothelin-1 production in rats with idiopathic pulmonary hypertension. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1992 ; Vol. 262, No. 5 6-5.
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