Bradykinin and capsaicin induced airways obstruction in the guinea pig are platelet dependent. (August 2015)

• Record Type: Journal Article
• Authors: Keir, S.D.; Spina, D.; Page, C.P.
• Is Part Of: Pulmonary pharmacology & therapeutics. Volume 33(2015:Aug.)
• Page Start: 25
• Page End: 31
• Publication Date: 2015-08
• Subjects: Platelets -- Bronchoconstriction -- Bradykinin -- Capsaicin -- Aggregation; RL Total lung resistance -- Cdyn Dynamic lung compliance -- TXA2 thromboxane -- TRPV1 transient receptor potential vanilloid 1 receptors -- PEG 400 Polyethylene glycol 400 grade -- PRP platelet rich plasma -- TPP transpulmonary pressure; Respiratory organs -- Diseases -- Chemotherapy -- Periodicals; 615.7205
• DOI: 10.1016/j.pupt.2015.05.004
• Languages: English
• ISSNs: 1094-5539

Abstract

Abstract: Introduction: 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. Conclusion: Airways obstruction induced by bombesin, capsaicin and bradykinin is platelet dependent, but not secondary to platelet aggregation.