P2872

         J Appl Physiol 1993 May;74(5):2380-6

        Respiratory and cardiovascular effects of inhaled and intravenous

        bradykinin, PGE2, and PGF2 alpha in dogs.

        Karlsson JA, Sant'Ambrogio FB, Forsberg K, Palecek F, Mathew OP,

        Sant'Ambrogio G.

        AB Draco, Pharmacology 1, Lund, Sweden.

        Prostaglandins (PGs) and bradykinin act as potent respiratory irritants

        in both normal and asthmatic subjects, but their sites of action are

        unknown. We compared the cardiorespiratory effects of bradykinin, PGE2,

        and PGF2 alpha nebulized into the isolated "in situ" larynx, inhaled

        into the tracheobronchial tree, and injected intravenously in

        anesthetized spontaneously breathing dogs. Laryngeal administration only

        resulted in a brief burst of rapid shallow breaths produced by

        bradykinin (1,000 micrograms/ml) in one of five dogs. Tracheobronchial

        administration of bradykinin (1,000 micrograms/ml) increased breathing

        rate and tidal volume (VT) in four of seven dogs without changing

        cardiovascular parameters, whereas PGE2 (500 micrograms/ml) caused

        similar effects in two of six dogs. Lower concentrations of both agents

        were essentially without effect. PGF2 alpha (50-500 micrograms/ml)

        inhaled into the lower airway increased breathing rate, reduced VT, and

        caused a concentration-dependent bronchoconstriction that was

        significantly reduced by atropine. Inhaled PGF2 alpha only slightly

        increased arterial blood pressure (5.8  2.8%) and heart rate (12.0

         6.4%). Intravenous PGF2 alpha (5 micrograms/kg) increased upper and

        lower airway resistances, which were accompanied by a decrease in

        breathing rate and VT, hypertension, and bradycardia. Bradykinin (1

        micrograms/kg) and PGE2 (1 and 3 micrograms/kg) produced apnea followed

        by rapid shallow breathing, bradycardia, and hypotension. These results

        indicate that the tracheobronchial tree is considerably more responsive

        to aerosolized bradykinin, PGE2, and PGF2 alpha than the laryngeal

        region. Moreover, the stronger effects produced by intravascular

        administration suggest a greater accessibility of rapidly adapting

        stretch receptors and C-fiber endings from the vascular bed than from

        the airway lumen.