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

¹ Institute of Surgical Research, ² Dept of Medical Informatics and Engineering and ³ Dept of Pathology, University of Szeged, Szeged, Hungary

CORRESPONDENCE: Z. Hantos, Dept of Medical Informatics and Engineering University of Szeged, H-6701, Szeged, P.O. Box 427, Hungary. Fax: 36 62544566

Keywords: airway resistance, endothelin-1, endothelin receptor antagonists, lung elastance, lung impedance, parenchymal resistance

Received: March 16, 2000
Accepted January 19, 2001

This study was supported by Hungarian Scientific Research Fund grants T30670 and T023089.

Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airways and parenchyma; however, the roles of the ET_A and ET_B receptors in the ET-1-induced changes in the airway and tissue compartments have not been fully explored.

Low-frequency pulmonary impedance (Z_L) was measured in anaesthetized, paralysed, open-chest guinea-pigs. Z_L spectra were fitted by a model to estimate airway resistance (R_aw) and inertance (I_aw), and coefficients of tissue damping (G) and elastance (H), and hysteresivity (=G/H).

Two successive doses of ET-1 (0.05 and 0.2 nmol·kg^–1) each evoked significant dose-related increases in R_aw, G, H and . Pretreatment with 20 nmol·kg^–1 BQ-610 (a highly selective ET_A 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·kg^–1 ETR-P1/fl (a novel ET_A receptor antagonist) or with 20 nmol·kg^–1 IRL 1038 (an ET_B 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.

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