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

The contributions of the airways and the parenchyma to the overall lung mec hanical response to endothelin-1 (ET-1) have not been systematically studie d, In this investigation, the ET-1 induced changes on lung mechanics in gui nea-pigs were separated into airway and parenchymal components. Pulmonary impedance (Z(L)) data were collected between 0.5 and 21 Hz in six anaesthetized, paralysed, open-chest animals by introducing small-amplitud e pseudorandom oscillations into the trachea through a wave tube. Z(L) was calculated before and following intravenous boluses of ET-1, with doses dou bled from 0.125-2 mu g.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 Z(L) spectra in each condition. Parenchymal hysteresis (eta) was calculated as G/H. After each dose, ET-1 induced significant increases in Raw (at peak respons e mean+/-SEM: 424+/-129%), G (400+/-80%), H (95+/-22%) and eta (156+/-33%), whereas law decreased following the two highest doses (-291+/-77%). These data suggest that the parenchymal constriction was accompanied by inh omogeneous constriction of the peripheral airways.