Effects of endothelin-1 on airway and parenchymal mechanics in guinea-pigs

The contributions of the airways and the parenchyma to the overall lung mechanical response to endothelin-1 (ET-1) have not been systematically studied. In this investigation, the ET-1 induced changes on lung mechanics in guinea-pigs were separated into airway and parenchymal components. Pulmonary impedance (ZL) data were collected between 0.5 and 21 Hz in six anaesthetized, paralysed, open-chest animals by introducing small-amplitude pseudorandom oscillations into the trachea through a wave tube. ZL was calculated before and following intravenous boluses of ET-1, with doses doubled from 0.125-2 microg x kg of body weight(-1). A model containing an airway resistance (Raw) and inertance (Iaw) and tissue damping (G) and elastance (H) was fitted to the ZL spectra in each condition. Parenchymal hysteresis (eta) was calculated as G/H. After each dose, ET-1 induced significant increases in Raw (at peak response mean+/-SEM: 424+/-129%), G (400+/-80%), H (95+/-22%) and eta (156+/-33%), whereas Iaw decreased following the two highest doses (-291+/-77%). These data suggest that the parenchymal constriction was accompanied by inhomogeneous constriction of the peripheral airways.