Differential roles of endothelin-1 ETA and ETB receptors and vasoactive intestinal polypeptide in regulation of the airways and the pulmonary vasculature in isolated rat lung

Tibor Janosi, Ferenc Peták, Fabienne Fontao, Denis R. Morel, Maurice Beghetti, Walid Habre

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15 Citations (Scopus)

Abstract

The available treatment strategies against pulmonary hypertension include the administration of endothelin-1 (ET-1) receptor subtype blockers (ET A and ETB 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 ETA blocker (BQ123), ETB blocker (BQ788), a combination of these selective blockers (ETA + ETB 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 (ZL) 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 ZL spectra. While VIP, ET A blocker and combined ETA and ETB blockers significantly prevented the pulmonary vasoconstriction induced by ET-1, ET B blockade enhanced the ET-1-induced increases in PVR. In contrast, the ETA and ETB 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 ETB blockers exert a differential effect between airway resistance and PVR.

Original languageEnglish
Pages (from-to)1210-1219
Number of pages10
JournalExperimental Physiology
Volume93
Issue number11
DOIs
Publication statusPublished - Nov 2008

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ASJC Scopus subject areas

  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)

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