Bradykinin receptor blockade does not affect oxygen-mediated pulmonary vasodilation in fetal lambs.
Both oxygenation and rhythmic stretching of the lungs are factors known to be responsible for pulmonary vasodilation at birth. Based on our previous studies, we proposed that the pulmonary vasodilation caused by oxygen could be mediated, at least in part, through bradykinin release. To test this hypothesis, we evaluated the cardiovascular responses to in utero ventilation during infusion of a B2-subtype bradykinin receptor antagonist (BKA), [N-adamantaneacetyl-D-Arg0,Hyp3,Thi5,8,D-Phe7]bradykinin, at 15-20 micrograms.kg-1.min-1 in eight near-term fetal lambs and during drug vehicle infusion in five control fetal lambs. Prostacyclin synthesis was inhibited by meclofenamate infusion (1.5 mg.kg-1.h-1). Surgical placement of vascular catheters, a flow transducer around the left pulmonary artery, and a tracheostomy tube and formalin infiltration of the ductus arteriosus to maintain its patency in the presence of meclofenamate were performed 72 h before the study. Hemodynamic variables and pulmonary blood flow were measured and pulmonary vascular resistance was calculated before and after in utero ventilation with 100% oxygen. Despite complete blockade by BKA of the pulmonary vasodilation produced by exogenous bradykinin, ventilation with oxygen significantly increased pulmonary blood flow by 676% over baseline state (157.8 +/- 66 to 1224 +/- 265 mL.min-1.100 g-1, p < 0.01) and decreased the pulmonary vascular resistance by 89% from baseline state (0.44 +/- 0.16 to 0.048 +/- 0.01 torr.mL-1.min.100 g, p < 0.01). Such responses to ventilation with oxygen were comparable to those noted in the control animals, in whom bradykinin receptors had not been blocked.(ABSTRACT TRUNCATED AT 250 WORDS)
Banerjee
A
A
Cardiovascular Research Institute, University of California, San Francisco 94143-0544.
Roman
C
C
Heymann
M A
MA
D000109:Acetylcholine / Q000494:pharmacology; D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D005260:Female; D005333:Fetus; D008168:Lung / Q000196:embryology / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology*; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D065168:Bradykinin Receptor Antagonists; C074544:bradykinin, 1-adamantanecarboxylic acid-Arg(0)-Hyp(3)-Thi(5,8)-Phe(7)-; D000109:Acetylcholine; D000218:Adamantane; D010100:Oxygen; D001920:Bradykinin