From the Research
Endothelin primarily causes bronchoconstriction in the airways. This is based on the fact that endothelin-1, the most potent isoform of the endothelin family, acts on specific receptors (primarily ETA and ETB receptors) in bronchial smooth muscle to induce contraction, leading to narrowing of the airways, as shown in a study published in the American Journal of Respiratory and Critical Care Medicine 1. The mechanism involves calcium mobilization within smooth muscle cells, triggering contraction, and endothelin also promotes inflammation and airway remodeling, further contributing to airway obstruction in chronic respiratory diseases. While endothelin can have complex effects in different tissues and under various conditions, its predominant action in the bronchial system is constriction rather than dilation, as supported by a study published in the journal Life Sciences 2. Some key points to consider include:
- Endothelin-1 is a potent bronchoconstrictor in asthma, with a bronchoconstrictor potency around 100 times that of methacholine in asthma, as demonstrated in a study published in the American Journal of Respiratory and Critical Care Medicine 1.
- Asthmatics exhibit bronchial hyperreactivity to endothelin-1, and inhaled endothelin-1 can safely be given to asthmatics and normal subjects in the nebulized dose range 0.96 to 15.36 nmol, as shown in a study published in the American Journal of Respiratory and Critical Care Medicine 1.
- Endothelin receptor antagonists have been investigated as potential therapeutic agents for asthma and other obstructive airway diseases, highlighting the importance of endothelin's role in bronchoconstriction. Overall, the evidence suggests that endothelin's primary effect in the airways is bronchoconstriction, making it a potential target for therapeutic intervention in respiratory diseases such as asthma.