Endothelins and the lung.

Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery

“…Thus ET-1 synthesis is regulated by synchronous expression and corresponds to the localization of ECE and its substrate big ET-1 in both endothelial cells and smooth muscle cells. Since ET-l is postulated to act primarily as a local modulator of vascular tone and ET receptors are expressed in endothelial and smooth muscle cells [1,2], ET-1 synthesized in the pulmonary artery may play both autocrine and paracrine roles in normal conditions and during the development of hypoxic pulmonary hypertension.…”

“…The actions of ET-l are mediated by two different receptors, ETA and ETB receptors [1,2]. ETA receptors are found in pulmonary vascular smooth muscle cells and mediate smooth muscle contraction and the proliferation of smooth muscle cells and fibroblasts, while ETB receptors are expressed in endothelial cells (ETB1 receptors) and smooth muscle cells (ETB2 receptors) and cause either relaxation or contraction, respectively [2,3,4]. Since the pulmonary vascular bed is complex in terms of regional differences in both structure and function, it is important to know about localization and distribution of ET-1 and ET receptors.…”

“…Since the pulmonary vascular bed is complex in terms of regional differences in both structure and function, it is important to know about localization and distribution of ET-1 and ET receptors. Although it is known that ET-1 is expressed in various cells including endothelial cells, epithelial cells, smooth muscle cells, and tissue macrophages in the lung [2,5,6], there are few studies showing the distribution of ET-1 and ECE expression along the axial pathways of the pulmonary artery.The over-expression of the messenger ribonucleic acid (mRNA) for ET-1, ETA and ETB receptors, and the overproduction of the ET-1 peptide in whole lung have been demonstrated in an experimental model of hypoxic pulmonary hypertension [6 -11]. Furthermore, blocking ETA receptors with selective antagonists attenuates the rise in pulmonary arterial pressure and the development of vascular remodelling associated with chronic hypoxia [12 -14].…”

“…Since the pulmonary vascular bed is complex in terms of regional differences in both structure and function, it is important to know about localization and distribution of ET-1 and ET receptors. Although it is known that ET-1 is expressed in various cells including endothelial cells, epithelial cells, smooth muscle cells, and tissue macrophages in the lung [2,5,6], there are few studies showing the distribution of ET-1 and ECE expression along the axial pathways of the pulmonary artery.…”

“…ET-l, a potent vasoconstrictor and smooth muscle mitogen composed of 21 amino acids, is synthesized from big ET-l by a specific cleavage at Trp 21 -Val 22 by ET converting enzyme (ECE) [l, 2]. The actions of ET-l are mediated by two different receptors, ETA and ETB receptors [1,2]. ETA receptors are found in pulmonary vascular smooth muscle cells and mediate smooth muscle contraction and the proliferation of smooth muscle cells and fibroblasts, while ETB receptors are expressed in endothelial cells (ETB1 receptors) and smooth muscle cells (ETB2 receptors) and cause either relaxation or contraction, respectively [2,3,4].…”