Prostaglandin F2 alpha (PGF2 alpha) and its synthetic analogue, fluprostenol, potently relaxed the precontracted isolated jugular vein of the rabbit (RJuV). The vasorelaxant activity of PGF2 alpha and fluprostenol was dependent upon an intact vascular endothelium. Although removal of the vascular endothelium abolished activity associated with PGF2 alpha-like agonists, it did not significantly alter the relaxant effects of prostaglandin E2 (PGE2). 2. The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), at 100 microM significantly inhibited the endothelium-dependent relaxations induced by PGF2 alpha. Lower doses (1 microM, 10 microM) of L-NAME had little or no effect. The relaxant effects of PGE2 were not affected by L-NAME (1-100 microM). D-NAME at 100 microM was without effect on the vasorelaxant responses to either PGF2 alpha or PGE2. 3. The potassium (K)-channel blockers tetraethylammonium (TEA, 1 mM), barium (1 mM) and quinine (100 microM), each tested in the presence of the inactive enantiomer D-NAME (100 microM) did not significantly affect the response to PGF2 alpha. Unexpectedly, both TEA and barium significantly and partially reversed the inhibitory effects of 100 microM L-NAME, whereas quinine had no effect. In similar studies, none of the three potassium channel blockers had any effect on relaxations elicited by PGE2 when given with D-NAME or L-NAME. 4. These results indicate that the PGF2 alpha-sensitive prostanoid receptors found in the vascular endothelium of the rabbit jugular vein are of the FP-receptor subtype. Nitric oxide (NO) appears to be the predominant messenger involved in PGF2 alpha-induced relaxation of the rabbit jugular vein. Potassium channels may have a minor role in mediating the vasorelaxation response to PGF2 alpha. When both NO synthesis and K-channels are simultaneously blocked, inhibition of PGF2 alpha-induced vasorelaxation by L-NAME is opposed by K-channel blockers. This diminution of the inhibitory effect of L-NAME by TEA and barium suggests that K-channels may possibly serve a compensatory role via the NO pathway.
