Premium
Differential roles of endothelin‐1 ET A and ET B receptors and vasoactive intestinal polypeptide in regulation of the airways and the pulmonary vasculature in isolated rat lung
Author(s) -
Janosi Tibor,
Peták Ferenc,
Fontao Fabienne,
Morel Denis R.,
Beghetti Maurice,
Habre Walid
Publication year - 2008
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2008.042481
Subject(s) - hypoxic pulmonary vasoconstriction , vasoactive intestinal peptide , endothelin 1 , vascular resistance , vasoconstriction , endothelin receptor , medicine , lung , airway resistance , pulmonary hypertension , vasodilation , endocrinology , receptor , cardiology , hemodynamics , neuropeptide
The available treatment strategies against pulmonary hypertension include the administration of endothelin‐1 (ET‐1) receptor subtype blockers (ET A and ET B antagonists); vasoactive intestinal polypeptide (VIP) has recently been suggested as a potential new therapeutic agent. We set out to investigate the ability of these agents to protect against the vasoconstriction and impairment of lung function commonly observed in patients with pulmonary hypertension. An ET A blocker (BQ123), ET B blocker (BQ788), a combination of these selective blockers (ET A + ET B blockers) or VIP (V6130) was administered into the pulmonary circulation in four groups of perfused normal rat lungs. Pulmonary vascular resistance (PVR) and forced oscillatory lung input impedance ( Z L ) were measured in all groups under baseline conditions and at 1 min intervals following ET‐1 administrations. The airway resistance, inertance, tissue damping and elastance were extracted from the Z L spectra. While VIP, ET A blocker and combined ET A and ET B blockers significantly prevented the pulmonary vasoconstriction induced by ET‐1, ET B blockade enhanced the ET‐1‐induced increases in PVR. In contrast, the ET A and ET B blockers markedly elevated the ET‐1‐induced increases in airway resistance, while VIP blunted this constrictor response. Our results suggest that VIP potently acts against the airway and pulmonary vascular constriction mediated by endothelin‐1, while the ET A and ET B blockers exert a differential effect between airway resistance and PVR.