Respiratory and cardiovascular effects of inhaled and intravenous bradykinin, PGE2, and PGF2 alpha in dogs.
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.
Karlsson
J A
JA
AB Draco, Pharmacology 1, Lund, Sweden.
Sant'Ambrogio
F B
FB
Forsberg
K
K
Palecek
F
F
Mathew
O P
OP
Sant'Ambrogio
G
G
D000280:Administration, Inhalation; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D009411:Nerve Endings / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D015237:Dinoprost; D015232:Dinoprostone; D001920:Bradykinin