[The role of endothelin-B receptors in hypoxic pulmonary hypertension].
Endothelin-1 (ET-1) is a potent vasoactive peptide, and is thought to play an important role in the regulation of pulmonary vascular tone. Previous studies suggested that ET-1 can act as a vasoconstrictor via the endothelin-A and -B 2 receptors located on smooth muscle cells, and also act as a vasodilator through the endothelin-B 1 receptor situated on endothelial cells in the pulmonary circulation. To determine the role of endothelin-B receptors in hypoxic pulmonary hypertension, we examined the hemodynamic effects of a selective endothelin-B receptor agonist (IRL 1620) in chronic hypoxic pulmonary hypertensive rats. In rat lungs perfused with a half-blood solution, vasoconstriction by KCl administration was gradually reversed by IRL 1620 in normoxic rats, but not in chronic hypoxic rats. In in vivo studies, small doses of IRL 1620 induced transient vasodilation in normoxic rats, but had no obvious effects in chronic hypoxic rats. A high dose of IRL 1620 mediated vasoconstriction only in chronic hypoxic rats. Endothelin-B receptor messenger-RNA expression was lower in the lungs of chronic hypoxic rats than in normoxic rats. These results suggested that although the vasodilatory response mediated by endothelin-B receptor can be expected to play a protective role in the development of pulmonary hypertension, that response is diminished in hypoxic pulmonary hypertension.
Hayashi
A
A
Department of Chest Medicine, Chiba University School of Medicine, Japan.
Tatsumi
K
K
Sugito
K
K
Igari
H
H
Kasahara
Y
Y
Kimura
H
H
Kuriyama
T
T
D000818:Animals; D016232:Endothelins / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
D016232:Endothelins; D010446:Peptide Fragments; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C074308:sovateltide