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 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.
Adamicza
A
A
Institute of Surgical Research, University of Szeged, Hungary.
Peták
F
F
Asztalos
T
T
Tiszlavicz
L
L
Boros
M
M
Hantos
Z
Z
D000403:Airway Resistance / Q000502:physiology*; D000818:Animals; D019332:Endothelin-1 / Q000502:physiology*; D006168:Guinea Pigs; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology*
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin