endothelin-1 and Airway-Obstruction

This review seeks to examine the potential contribution of the recently discovered peptide endothelin-1 to the pathophysiology of asthma. The actions of endothelin-1 which mimic features of asthma, the evidence for increased production of endothelin-1 in asthma and the potential for asthma therapy based on modification of the activity of endothelin-1 are reviewed.

Topics: Airway Obstruction; Animals; Asthma; Bronchial Provocation Tests; Endothelin Receptor Antagonists; Endothelin-1; Humans; Inflammation; Mucous Membrane

Endothelin-1 (ET-1) expression is increased after lung transplantation in association with ischemia reperfusion injury and acute rejection. However, little is known of the role of ET-1 during the development of obliterative bronchiolitis. In this study, we investigated the biological significance of ET-1 in obliterative airway disease development using a rat tracheal allograft model. Immunoreactivity of ET-1 and its receptors ET-RA and ET-RB was increased four-fold in allografts compared with syngrafts and localized to mononuclear cells and smooth muscle cells of the myofibroproliferative lesion and airway wall, indicating that ET-1 may mediate its effects in both a paracrine and autocrine manner in smooth muscle cells. Inhibition of ET-1 action by a nonselective ET-1 receptor antagonist, bosentan, significantly decreased tracheal occlusion, which was linked to delayed epithelial necrosis, suppressed smooth muscle cell proliferation, and a marked reduction in the number of interleukin-1beta and interleukin-2 immunoreactive cells. Our findings show that endogenous ET-1 activation is associated with obliteration of the airway wall, and blocking signaling downstream of ET-1 receptors leads to attenuation of obliterative airway disease. The results suggest that ET-1 has a proproliferative and proinflammatory role in the development of obliterative bronchiolitis.

Topics: Airway Obstruction; Animals; Antihypertensive Agents; Bosentan; Bronchiolitis Obliterans; Endothelin-1; Lung Transplantation; Male; Rats; Receptors, Endothelin; Sulfonamides; Trachea

Endothelin (ET)-1 is a potent vasoconstrictive and mitogenic peptide produced by endothelial cells and degraded predominantly in pulmonary vasculature. We measured ET-1 in 9-normotensive and 14 hypertensive men with obstructive sleep apnea. The ET-1 levels were higher in both normotensive (mean +/- SD, 6.3 +/- 2.8 pg/ml) and hypertensive (7.8 +/- 3.0 pg/ml) groups than in 66 healthy controls (2.9 +/- 1.2 pg/ml). Ten patients were restudied after three months of nCPAP treatment. No decrease in ET-1 was observed.

Topics: Adult; Airway Obstruction; Endothelin-1; Endothelium, Vascular; Humans; Hypertension; Male; Middle Aged; Obesity; Polysomnography; Positive-Pressure Respiration; Sleep Apnea Syndromes