title: Bradykinin and capsaicin induced airways obstruction in the guinea pig are platelet dependent.
abstract: BACKGROUND
  Airways obstruction induced by intravenously administered bradykinin is abolished in guinea pigs treated with indomethacin, which has been shown to be, at least in part thromboxane dependent. As thromboxane is primarily generated from circulating platelets, we investigated whether airways obstruction induced by bradykinin, and other spasmogens, is platelet dependent and the role platelet aggregation played in this response.
  
  
  METHODS
  Guinea pigs were chronically treated with busulfan to induce thrombocytopenia. Total lung resistance was measured in anaesthetised and mechanically ventilated control and thrombocytopaenic animals to various stimuli that induce airways obstruction. In other experiments, platelet aggregation was assessed in vitro in response to the same stimuli: guinea pigs were anaesthetized, blood was collected and centrifuged to generate firstly platelet-rich plasma and then platelet-poor plasma. Platelets were resuspended in HEPES buffer and platelet aggregation was assessed.
  
  
  RESULTS
  Busulfan treatment significantly reduced the number of circulating platelets in guinea-pigs by 85.5%, but had no significant effect on the number of circulating leukocytes. Treatment with busulfan had no significant effect on bronchoconstriction induced by the direct acting spasmogens histamine or methacholine. However, platelet depletion significantly increased airways obstruction induced by Substance P, but caused a significant reduction in airways obstruction induced by bradykinin, bombesin or capsaicin (P < 0.05). None of these stimuli however were able to exhibit a direct effect on platelet aggregation in vitro. Moreover, busulfan did not significantly alter the contractility of guinea-pig isolated trachea in response to capsaicin.
  
  
  CONCLUSIONS
  Airways obstruction induced by bombesin, capsaicin and bradykinin is platelet dependent, but not secondary to platelet aggregation.
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, 5th Floor Franklin Wilkins Building, Waterloo Campus, London, SE1 9NH, UK.
authors.forename: S D
authors.initials: SD
authors.lastname: Keir
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, 5th Floor Franklin Wilkins Building, Waterloo Campus, London, SE1 9NH, UK.
authors.forename: D
authors.initials: D
authors.lastname: Spina
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, 5th Floor Franklin Wilkins Building, Waterloo Campus, London, SE1 9NH, UK. Electronic address: clive.page@kcl.ac.uk.
authors.forename: C P
authors.initials: CP
authors.lastname: Page
mesh_terms: D000402:Airway Obstruction / Q000139:chemically induced*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001839:Bombesin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D002066:Busulfan / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010974:Platelet Aggregation / Q000502:physiology; D013921:Thrombocytopenia / Q000139:chemically induced; D014132:Trachea / Q000187:drug effects
chemical_list: D016210:Methacholine Chloride; D006632:Histamine; D002066:Busulfan; D001839:Bombesin; D002211:Capsaicin; D001920:Bradykinin
keywords: Aggregation; Bradykinin; Bronchoconstriction; Capsaicin; Platelets