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The actions of bradykinin and lys-bradykinin on tracheal blood flow and smooth muscle in anaesthetized sheep
Affiliation:1. University of British Columbia, School of Kinesiology, 210-6081 University Boulevard, Vancouver, BC, Canada V6T 1Z1;2. University of British Columbia, Institute for Resources, Environment and Sustainability, 2202 Main Mall, Vancouver, BC, Canada V6T 1Z1;1. Nanobiomaterials Laboratory, Institute of Applied Biotechnology (CINDEFI, CONICET-UNLP, CCT La Plata), Dept. of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47 y 115, CP 1900 La Plata, Argentina;2. LUNAM, Université d’Angers, UMR S-1066, Micro-Nanomédecines Biomimétiques, IBS Institut de Biologie en Santé, Batiment IRIS, 4 rue Larrey, 49933 Angers Cedex 9, France;3. Chemical Inorganic Center (CEQUINOR, CONICET CCT La Plata) – School of Sciences – Universidad Nacional de La Plata (UNLP), La Plata CP 1900, Argentina;4. LUNAM, Université du Maine, Institut des Molécules et Matériaux du Mans, UMR CNRS 6283, Avenue Olivier Messiaen, 72085 Le Mans Cedex 9, France;1. Key Laboratory for Organic Electronics & Information Displays (KLOEID), Institute of Advanced Materials (IAM), and School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210046, China;2. Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 2019 Jialuo Road, Shanghai 201800, China;3. Pulmonary Medcine Department, Zhongshan Hospital, 180 Fenglin Road, Shanghai 200032, China;1. Yale Adult Cystic Fibrosis Program, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine;2. Division of Respiratory Medicine, Translational Medicine, University of Toronto Hospital for Sick Children, 555 University Avenue, Toronto Ontario M5G 1X8, Canada;3. Cystic Fibrosis Foundation, Bethesda, MD, USA;1. Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel;2. Division of Neonatology and Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Abstract:The actions of bradykinin and the related compound lys-bradykinin have been studied on the tracheal circulation and tracheal smooth muscle of the sheep. Cranial tracheal arteries of ten anaesthetised and paralysed sheep were isolated and perfused at systemic arterial pressure; arterial inflow was measured with an electromagnetic flow probe. Tracheal smooth muscle tone was assessed by measuring the external diameter of the cranial trachea. Close arterial injection of bradykinin and lys-bradykinin (0.1 to 1000 pmoles) produced potent dose-dependent falls in tracheal vascular resistance: for bradykinin a maximum fall of −56.4% (52.3–60.5%, 95% confidence interval) and for lys-bradykinin −52.8% (46.5–59.1%). The ED50 values were 0.69 (0.51–1.32) and 1.46 (1.19–2.28) pmoles respectively. Small and inconsistent relaxation of tracheal smooth muscle was seen with the higher doses (> 1.9 pmoles) of both kinins. Intravenous indomethacin (5mg.kg−1) increased the vasodilation produced by bradykinin and lys-bradykinin. Oxyhaemoglobin (4 μm at 0.35ml.min−1) infused into the tracheal circulation almost abolished the responses to bradykinin and methacholine. The results indicate that in the sheep trachea bradykinin has little action on airway smooth muscle but is a potent dilator of the vasculature; bradykinin and lys-bradykinin are of similar potency suggesting the action may be via B2 receptors. While the vascular responses may be modulated by vasoconstrictor cyclo-oxygenase products the vasodilation is likely to be endothelium-dependent and not prostanoid-mediated.
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