Microsphere-induced bronchial artery vasodilation: role of adenosine, prostacyclin, and nitric oxide.
We previously found that injection of 15-micron microspheres into the bronchial artery of sheep decreased bronchial artery resistance. This effect was inhibited partially by indomethacin or 8-phenyltheophylline, suggesting that microspheres caused release of a dilating prostaglandin and adenosine. To identify the prostaglandin and confirm adenosine release, we perfused the bronchial artery in anesthetized sheep. In 12 sheep, bronchial artery blood samples were obtained before and after the infusion of 1 x 10(6) microspheres or microsphere diluent into the bronchial artery. Microspheres, but not diluent, decreased bronchial artery resistance by 40% and increased bronchial artery plasma 6-ketoprostaglandin F1 alpha (194.7 +/- 45.0 to 496.5 +/- 101.3 pg/ml), the stable metabolite of prostacyclin, and prostaglandin (PG) F2 alpha (28.1 +/- 4.4 to 46.2 +/- 9.7 pg/ml). There were no changes in PGD2, PGE2, thromboxane B2, adenosine, inosine, or hypoxanthine. Pretreatment with dipyridamole, an adenosine uptake inhibitor, did not affect bronchial artery nucleoside concentrations (n = 7). Microsphere-induced vasodilation was not enhanced by dipyridamole (n = 9) and was not inhibited by either the adenosine receptor antagonist xanthine amine congener (n = 4) or the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (n = 8). These results do not support a role for either adenosine or NO and suggest that microspheres caused bronchial artery vasodilation through release of prostacylin and an unidentified vasodilator.
Pearse
D B
DB
Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21224, USA.
Dahms
T E
TE
Wagner
E M
EM
D000227:Adenine Nucleotides / Q000097:blood; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001981:Bronchial Arteries / Q000187:drug effects*; D004176:Dipyridamole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood; D008863:Microspheres; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000227:Adenine Nucleotides; D004791:Enzyme Inhibitors; D014970:Xanthines; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019344:Lactic Acid; D004176:Dipyridamole; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D000241:Adenosine