Vascular actions of arachidonic acid and its metabolites in perfused mesenteric and femoral beds of the dog.

The effects of arachidonate and its major metabolites were examined in vascular beds perfused via the femoral and mesenteric arteries of chloralose-anaesthetised dogs. Close intra-arterial injection of prostacyclin (PGI2, 0.02--2 microgram), PGE2 (0.05--1 microgram) and their precursors, the endoperoxide PGH2 (0.5--2 microgram) and sodium arachidonate (100--550 microgram), all induced vasodilatation. Sodium linoleate (500 microgram) was inactive. Prostacyclin was equally active in both vascular beds, but PGE2 was more potent in the femoral and less so in the mesenteric bed. PGH2 was of similar potency to prostacyclin in both beds, but 6-oxo-PGF 1 alpha (10--100 microgram) was inactive. Thromboxane A2 (TXA2, 1--2 microgram) was a potent vasoconstrictor of the mesenteric bed, but not the femoral bed, although the endoperoxide analogue U46619 was vasocontrictor in both vasculatures. Fatty acid hydroperoxides did not specifically modify the vasodilator effects of PGH2 or arachidonate, presumably because these inhibitors are rapidly reduced in vivo. Indomethacin and meclofenamate potentiated vasodilatation induced by prostacyclin or endoperoxide, but reduced or abolished that caused by arachidonate. The rise in perfusion pressure induced by TXA2 was potentiated and prolonged by indomethacin. Inhibition of synthesis of endogenous prostacyclin, by exacerbating the vasoconstrictor action of TXA2, may have contributed to this effect.