Effect of endothelin-1 on respiratory neural drive and diaphragmatic activity in the pigs

The study was performed in twelve anesthetized spontaneously breathing pigs, divided into two groups. In the animals of group 1 we evaluated the effects of ET-1 administered by aerosol (200 pmol/kg in 1 ml of saline solution) on respiratory neural drive and on diaphragmatic activity. In the animals of group 2, to study the effects of ET-1 in the absence of arachidonic acid metabolites, the peptide was administered after pretreatment with indomethacin (3 mg/kg i.v.). Tracheal pressure (P0.5), obtained during the inspiratory effort was evaluated as an index of respiratory output and VT/TI ratio as an index of vagal input. Costal and crural electromyograms were recorded and avaluated as moving-average/inspiratory time ratio (DeltaEMG/TI), which is an index of neuromuscular drive, and as power spectrum quantified as centroid frequency (Cf). Our results show that in normal pigs ET-1 increases the Cf of crural diaphragm, without changing neuromuscular drive, while in pigs pretreated with indomethacin the peptide increases the Cf of the crural and costal portions of the diaphragm. These last responses are due to a modest excitatory effect on neural drive that is correlated with ET-1-dependent bronchoconstriction.These results further suggest that in the presence of prostanoids ET-1 recruits new crural fibers, while in the absence of prostanoids the recruitment involves the costal portion too. This mechanism is important to assure respiratory function in presence of bronchoconstriction through adequate diaphragmatic activity.