title: Regulation of microvascular prostacyclin and thromboxane with inhibitors of arachidonic acid metabolism.
abstract: The levels of the stable degradation products of prostacyclin (PGI2) and thromboxane A2 (TXA2): 6-oxo-prostaglandin E1 alpha (6-oxo-PGE1 alpha) and thromboxane B2 (TXB2) respectively were determined in the effluent of the rabbit epigastric skin flap after infusion of exogenous arachidonic acid. The blood to the flap passes through the microcirculation and thus the changes in eicosanoid biosynthesis in this part of the vasculature were recorded. The aim was to use inhibitors of arachidonic acid metabolism to increase the PGI2/TXA2 ratio. This may be potentially beneficial to ischaemic skin flaps by reducing platelet aggregation associated with damaged microvascular endothelium, overcoming vasospasm and increasing microvascular blood flow. Increased PGI2/TXA2 ratios (up to 5-fold) were best achieved using TXA2 synthetase inhibitors such as dazoxiben hydrochloride. These were significantly more potent than the phosphodiesterase inhibitor dipyridamole, and the lipoxygenase inhibitor Bay g6575. No increase in blood flow was achieved. The cyclooxygenase inhibitor indomethacin did slow the blood flow at high concentrations (above 10(-5) M), and inhibited both PGI2 and TXA2 synthesis. Approximately 2-fold higher concentrations of dazoxiben hydrochloride and dipyridamole were required to produce the same TXA2 synthetase inhibition in the flap microvasculature in vivo compared with platelets in vitro.
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000097:blood*; D011464:Epoprostenol / Q000097:blood*; D008833:Microcirculation; D010974:Platelet Aggregation; D011817:Rabbits; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D013928:Thromboxane A2 / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D001095:Arachidonic Acids; D013929:Thromboxane B2; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase