Endothelin in cardiopulmonary disease: factor paracrine vs neurohumoral

Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide which also has important growth promoting effects on other cellular elements of the vascular wall. Increased local expression and release of endothelin-1 may therefore contribute to abnormal vascular tone and structure in paracrine fashion. Evidence of increased pulmonary production of endothelin-1 by the lung in patients with primary pulmonary hypertension is reviewed, including increased release across the pulmonary circulation and increased vascular expression of the peptide and its mRNA. However, circulating endothelin-1 might also have a humoral action on distant vascular beds. Changes in plasma endothelin-1 in response to postural change and chronic heart failure support a role for this potent vasoconstrictor factor in the neurohumoral response to haemodynamic stress. Thus, like other vascular regulatory mechanisms, the endothelin system might play a dual role in the control of vascular function with both local tissue and circulatory components.