Stimulation of afferent vagal endings in the intrapulmonary airways by prostaglandin endoperoxide analogues

Two cyclic ether (CE) analogues of the prostaglandin endoperoxide PGH₂, CE I and CE II, have been found to exert powerful stimulant effects on lung ‘irritant’ receptors and bronchial C-fiber endings after intravascular or aerosol administration in open-chest dogs under Dial-pentobarbital anesthesia. ‘Irritant’ receptors responded to a dose as small as 0.1 μg/kg CE II, injected into the right atrium. CE II was twice as effective as CE I and 10–20 times more potent than PGF_2α. As an aerosol, it exceeded histamine in potency by more than 800 times. ‘Irritant’ receptor stimulation was always associated with decrease in lung compliance and increase in lung resistance. Isoproterenol which reduced the latter effects also diminished the response of ‘irritant’ receptors. Left atrial injection of GE_S had only weak and delayed effects. CE-induced ‘irritant’ receptor firing declined or ceased during ventilatory arrest in expiration and following hyperinflation of the lungs. In contrast to ‘irritant’ receptors, C-fibers responded more effectively and more rapidly, and in the absence of mechanical changes, when the drugs were injected into the left atrium as compared to right atrial injection. These findings suggest that CE-induced ‘irritant’ receptor stimulation is secondary to changes in lung mechanics, whereas C-fiber stimulation is a direct effect upon the nerve ending.