MICROSPHERE-INDUCED BRONCHIAL ARTERY VASODILATION - ROLE OF ADENOSINE, PROSTACYCLIN, AND NITRIC-OXIDE

We previously found that injection of 15-mu m microspheres into the br onchial artery of sheep decreased bronchial artery resistance. This ef fect was inhibited partially by indomethacin or 8-phenyltheophylline, suggesting that microspheres caused release of a dilating prostaglandi n and adenosine. To identify the prostaglandin and confirm adenosine r elease, we perfused the bronchial artery in anesthetized sheep. In 12 sheep, bronchial artery blood samples were obtained before and after t he infusion of 1 x 10(6) microspheres or microsphere diluent into the bronchial artery. Microspheres, but not diluent, decreased bronchial a rtery resistance by 40% and increased bronchial artery plasma 6-ketopr ostaglandin F-1 alpha (194.7 +/- 45.0 to 496.5 +/- 101.3 pg/ml), the s table metabolite of prostacyclin, and prostaglandin (PG) F-2 alpha (28 .1 +/- 4.4 to 46.2 +/- 9.7 pg/ml). There were no changes in PGD(2), PG E(2), thromboxane B-2, adenosine, inosine, or hypoxanthine. Pretreatme nt with dipyridamole, an adenosine uptake inhibitor, did not affect br onchial artery nucleoside concentrations (n = 7). Microsphere-induced vasodilation was not enhanced by dipyridamole (n = 9) and was not inhi bited by either the adenosine receptor antagonist xanthine amine conge ner (n = 4) or the nitric oxide (NO) synthase inhibitor N-G-monomethyl -L-arginine (n = 8). These results do not support a role for either ad enosine or NO and suggest that microspheres caused bronchial artery va sodilation through release of prostacylin and an unidentified vasodila tor.