Studies on the Regulation of Secretion in Clara Cells with Evidence for Chemical Nonautonomic Mediation of the Secretory Response to Increased Ventilation in Rat Lungs

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Abstract
Using EM and morphometric methods to assess secretion, 2 times tidal volume ventilation of isolated perfused rat lung stimulates secretion by bronchiolar Clara cells; this effect is not prevented by .beta.-adrenergic blockade. The isolated perfused rat lung and the anesthetized, mechanically ventilated rat were used to further study the mechanism by which large tidal volumes stimulate secretion by Clara cells. The perfused lung showed that .alpha.-adrenergic inhibition did not block the secretory effect of ventilation at 2 times normal tidal volume; indomethacin completely blocked the secretory action of 2 times tidal volume ventilation; medium previously used to perfuse lungs ventilated at 2 times tidal volume, but not medium previously used to ventilate lungs at normal tidal volume, stimulated secretion by Clara cells when used to perfuse fresh lungs ventilated at tidal volume, and addition of prostacyclin to the fresh perfusate increased secretion by Clara cells of lungs ventilated at normal tidal volume. In anesthetized, mechanically ventilated rats, sighs stimulated secretion by Clara cells; this increased secretion was inhibited by indomethacin but not by cholinergic blockade (bilateral vagotomy). Increased volume ventilation apparently stimulates secretion by Clara cells in vivo and in vitro; chemical nonadrenergic, noncholinergic mechanisms are evidently involved in this secretion, and prostaglandins may be the chemical messenger coupling the mechanico-secretory events.