Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation.

Abstract

BACKGROUND To elucidate the pathophysiological significance of endothelin in pulmonary hypertension associated with congenital heart defects, we measured plasma endothelin-like immunoreactivity (ET-LI) concentrations by using radioimmunoassay in 18 patients with pulmonary hypertension (PH group; age, 6 months to 12 years) in comparison with 27 patients without pulmonary hypertension (non-PH group; age, 6 months to 12 years). METHODS AND RESULTS Blood samples were obtained from the vena cava, right atrium, right ventricle, left or right pulmonary artery, and pulmonary vein or the pulmonary arterial wedge position (pulmonary venous blood) during cardiac catheterization. Plasma ET-LI concentrations in the PH group were significantly higher than those in the non-PH group at all sampling sites. In the PH group, plasma ET-LI concentration showed a significant increase between the right ventricle and pulmonary artery and between the pulmonary artery and pulmonary vein. The increment of plasma ET-LI concentrations from the right ventricle to the pulmonary vein was significantly larger in the PH group than in the non-PH group and was significantly correlated with pulmonary artery pressure. CONCLUSIONS Plasma ET-LI concentrations were elevated in patients with pulmonary hypertension; the elevation was due to the increased production of ET-LI in pulmonary circulation, indicating the possible involvement of endothelin in the pathophysiology of pulmonary hypertension.

ETA receptors are the primary mediators of myofilament calcium sensitization induced by ET‐1 in rat pulmonary artery smooth muscle: a tyrosine kinase independent pathway

“…As mentioned previously, the second phase of acute HPV requires the release of a vasoconstrictor from the intact endothelium (Leach et al, 1994) and appears to develop in the presence of a constant cytoplasmic free Ca 2+ concentration . Moreover, recent investigations have suggested that ET-1 may play an important role in the regulation of pulmonary vascular tone and may promote the development of hypoxic pulmonary hypertension (Chen et al, 1997;Bonvallet et al, 1994;Prie et al, 1997;Langleben et al, 1993;Yoshibayashi et al, 1991). Our ®ndings suggest, therefore, that ET-1, or a related peptide, may be responsible for the increase in myo®lament Ca 2+ sensitivity associated with hypoxic pulmonary hypertension.…”

“…Recent investigations have suggested that ET-1 may play an important role in the regulation of pulmonary vascular tone and may promote the development of pulmonary hypertension (Chen et al, 1997;Bonvallet et al, 1994;Prie et al, 1997;Langleben et al, 1993;Yoshibayashi et al, 1991). During pulmonary hypoxia, plasma ET-1 levels are elevated due to increased expression of ET-1 mRNA, and release of ET-1 from pulmonary artery endothelial cells (Giaid et al, 1993;Elton et al, 1992;Li et al, 1994a;, and this is accompanied by an increase in endothelin receptor gene expression in human and rat pulmonary vasculature (Li et al, 1994a,b).…”

Endothelin: setting the scene in PAH

“…ET-1 induces endothelial cell, smooth muscle cell and fibroblast dysfunction, as well as cytokine release, and is thus well recognised as playing a central role in the complex pathogenesis of PAH. Supporting evidence of the involvement of ET-1 and activation of the ET system in PAH pathogenesis came from observations that plasma levels of ET-1 are three to four times the upper limit of normal in patients with several types of PAH, including idiopathic PAH (iPAH) [6], PAH related to connective tissue disease [7], PAH secondary to congenital heart disease [8] and PAH secondary to HIV infection [9]. More important than absolute levels of ET-1 in the plasma, however, is the observation that ET-1 levels are elevated locally in all vessels of the pulmonary vasculature ( fig.…”

Lung Function, Inflammation, and Endothelin‐1 in Congenital Heart Disease–Associated Pulmonary Arterial Hypertension

“…Endothelin‐1 is a vasoconstrictor that is found in elevated levels in CHD‐APAH and contributes to the development of PAH49 and is a potent bronchoconstrictor. Thus, it was hypothesized that endothelin‐1 could play a key role in airway obstruction in CHD‐APAH patients 50.…”