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

Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airw ays 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 fu lly explored. Low-frequency pulmonary impedance (ZL) was measured in anaesthetized, paral ysed, open-chest guinea-pigs. ZL spectra were fitted by a model to estimate airway resistance (Raw) and inertance (law), and coefficients of tissue da mping (G) and elastance (H), and hysteresivity (eta = G/H). Two successive doses of ET-1 (0.05 and 0.2 nmol.kg(-1)) each evoked signifi cant dose-related increases in Raw, G, H and eta. Pretreatment with 20 nmol .kg(-1) BQ-610 (a highly selective ETA receptor antagonist) resulted in a s ignificantly decreased elevation only in H after the lower dose of ET-1. Ho wever, all parameters changed significantly less on the administration of E T-1 after pretreatment with 80 nmol.kg(-1) BQ-610, with 20 nmol.kg(-1) ETR- P1/fl (a novel ETA receptor antagonist) or with 20 nmol.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 v ia stimulation of both receptor types in both compartments.