RESPIRATORY AND CARDIOVASCULAR EFFECTS OF INHALED AND INTRAVENOUS BRADYKININ, PGE(2), AND PGF(2-ALPHA) IN DOGS

Prostaglandins (PGs) and bradykinin act as potent respiratory irritant s in both normal and asthmatic subjects, but their sites of action are unknown. We compared the cardiorespiratory effects of bradykinin, PGE 2, and PGF2alpha nebulized into the isolated ''in situ'' larynx, inhal ed into the tracheobronchial tree, and injected intravenously in anest hetized spontaneously breathing dogs. Laryngeal administration only re sulted in a brief burst of rapid shallow breaths produced by bradykini n (1,000 mug/ml) in one of five dogs. Tracheobronchial administration of bradykinin (1,000 mug/ml) increased breathing rate and tidal volume (V(T)) in four of seven dogs without changing cardiovascular paramete rs, whereas PGE2 (500 mug/ml) caused similar effects in two of six dog s. Lower concentrations of both agents were essentially without effect . PGF2alpha (50-500 mug/ml) inhaled into the lower airway increased br eathing rate, reduced V(T), and caused a concentration-dependent bronc hoconstriction that was significantly reduced by atropine. Inhaled PGF 2alpha only slightly increased arterial blood pressure (5.8 +/- 2.8%) and heart rate (12.0 +/- 6.4%). Intravenous PGF2alpha (5 mug/kg) incre ased upper and lower airway resistances, which were accompanied by a d ecrease in breathing rate and V(T), hypertension, and bradycardia. Bra dykinin (1 mug/kg) and PGE2 (1 and 3 mug/kg) produced apnea followed b y rapid shallow breathing, bradycardia, and hypotension. These results indicate that the tracheobronchial tree is considerably more responsi ve to aerosolized bradykinin, PGE2, and PGF2alpha than the laryngeal r egion. Moreover, the stronger effects produced by intravascular admini stration suggest a greater accessibility of rapidly adapting stretch r eceptors and C-fiber endings from the vascular bed than from the airwa y lumen.