Hypoxia-induced change in prostanoids production and coronary flow in isolated rat heart.

The contribution of prostanoids to the change in coronary flow induced by hypoxia was examined in Langendorff-perfused rat heart. In the coronary effluent, 5 prostanoids, i.e., prostaglandins (PGs) D2, E2, and F2 alpha, 6-keto PGF1 alpha and thromboxane (TX) B2, were quantified by GC/MS, whereas PGA2, B2, and E1 were not detected under any conditions. During hypoxia, coronary flow initially increased to 189.5 +/- 17.8% of the control, and at the same time release of all PGs, except for TXB2, increased significantly (6-keto PGF1 alpha: from 3.57 +/- 0.98 to 5.54 +/- 1.25 pmol/min.g, D2: from 1.47 +/- 0.26 to 2.22 +/- 0.26 pmol/min.g, E2: from 0.27 +/- 0.08 to 0.96 +/- 0.21 pmol/min.g, F2 alpha: from 0.23 +/- 0.09 to 0.48 +/- 0.13 pmol/min.g, TXB2: from 0.61 +/- 0.10 to 0.58 +/- 0.15 pmol/min.g). During the later phase (10-20 min) of hypoxia, coronary flow decreased without concomitant decrease in the release of PGs. The administration of indomethacin (10 microM) and aspirin (1 mM) did not affect the normoxic coronary flow. However, during the early phase of hypoxia, they significantly suppressed the increase in coronary flow. Administration of arachidonic acid (1 mg/l) increased PG release 6.4-12.5-fold and increased coronary flow to 176.1 +/- 6.5% of the control level. In the presence of arachidonic acid, there was a good correlation between the coronary flow and the amount of released vasodilative PGs (PGE2 and 6-keto PGF1 alpha), suggesting the contribution of these PGs to coronary vasoregulation. On the other hand, when hearts were made hypoxic in the presence of arachidonic acid, percentage increase in PG release was much reduced, and similarly, coronary flow was not elevated. These results indicate that the increase in coronary flow during the early phase of hypoxia is mediated, at least in part, by the increased release of vasodilative PGs.