Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors

• Published in: The European respiratory journal Vol. 17; no. 5; pp. 975 - 981
• Main Authors: Adamicza, A, Petak, F, Asztalos, T, Tiszlavicz, L, Boros, M, Hantos, Z
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01.05.2001; Maney
• Subjects: Air breathing; Airway Resistance - physiology; Animals; Biological and medical sciences; Endothelin-1 - physiology; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin - physiology; Respiratory Mechanics - physiology; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Vertebrates: respiratory system; Pharmacologic test; Peptide hormone; Rodentia; Parenchyma; Exploration; Endothelin 1; Respiratory system; Biological activity; Respiratory tract; Vertebrata; Mammalia; Guinea pig; Animal; Vasoconstrictor agent; Antagonist; Comparative study; Biological receptor
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.01.17509750

Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airways and parenchyma; however, the roles of the ETA and ETB receptors in the ET-1-induced changes in the airway and tissue compartments have not been fully explored. Low-frequency pulmonary impedance (ZL) was measured in anaesthetized, paralysed, open-chest guinea-pigs. ZL spectra were fitted by a model to estimate airway resistance (Raw) and inertance (Iaw), and coefficients of tissue damping (G) and elastance (H), and hysteresivity (eta = G/H). Two successive doses of ET-1 (0.05 and 0.2 nmol x kg(-1)) each evoked significant dose-related increases in Raw, G, H and eta. Pretreatment with 20 nmol x kg(-1) BQ-610 (a highly selective ETA receptor antagonist) resulted in a significantly decreased elevation only in H after the lower dose of ET-1. However, all parameters changed significantly less on the administration of ET-1 after pretreatment with 80 nmol-kg(-1) BQ-610, with 20 nmol x kg(-1) ETR-P1/fl (a novel ETA receptor antagonist) or with 20 nmol x kg(-1) IRL 1038 (an ETB receptor antagonist). The results of the separate assessments of the airway and tissue mechanics demonstrate that endothelin-1 induces airway and parenchymal constriction via stimulation of both receptor types in both compartments.