Endothelin involvement in respiratory centre activity

To evaluate the role of endothelin (ET) in respiratory homeostasis we studi ed the effects of the ETA and ETB receptor blocking agent bosentan on respi ratory mechanics and control in seven anaesthetised spontaneously breathing pigs, for 180 min after single bolus administration (20 mg/kg i.v.). The r esults show that the block of ETreceptors induced a significant increase in compliance and decrease in resistance of the respiratory system, entailing a significant reduction of diaphragmatic electromyographic activity, witho ut affecting the centroid frequency of the power spectrum. Bosentan adminis tration induced a significant increase in tidal volume (V-T) accompanied by a significant decrease in respiratory frequency, without any significant c hange in pulmonary ventilation, CO2 arterial blood gas pressure or pH. Sinc e the relationship between V-T and inspiratory time remained substantially constant after bosentan administration, the changes in respiratory pattern appear to be the result of an upward shift in inspiratory off-switch thresh old. Both inspiratory and expiratory times during occluded breathing were i ncreased by block of ETreceptors, suggesting also a central respiratory neu romodulator effect of ET. In conclusion the present results suggest that th e block of ETreceptors in spontaneously breathing pigs exerts a role on mec hanical properties of the respiratory system as well as on peripheral and c entral mechanisms of breathing control. (C) 2001 Harcourt Publishers Ltd.