Identification of a prostanoid FP receptor population producing endothelium-dependent vasorelaxation in the rabbit jugular vein

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Abstract
1 Prostaglandin F2α (PGF2α) and its synthetic analogue, fluprostenol, potently relaxed the precontracted isolated jugular vein of the rabbit (RJuV). The vasorelaxant activity of PGF2α and fluprostenol was dependent upon an intact vascular endothelium. Although removal of the vascular endothelium abolished activity associated with PGF2α-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 μm significantly inhibited the endothelium-dependent relaxations induced by PGF2α. Lower doses (1 μm, 10 μm) of l-NAME had little or no effect. The relaxant effects of PGE2 were not affected by l-NAME (1–100 μm). D-NAME at 100 μm was without effect on the vasorelaxant responses to either PGF2α or PGE2. 3 The potassium (K)-channel blockers tetraethylammonium (TEA, 1 mm), barium (1 mm) and quinine (100 μm), each tested in the presence of the inactive enantiomer D-NAME (100 μm) did not significantly affect the response to PGF2α. Unexpectedly, both TEA and barium significantly and partially reversed the inhibitory effects of 100 μm 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 PGF2α-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 PGF2α-induced relaxation of the rabbit jugular vein. Potassium channels may have a minor role in mediating the vasorelaxation response to PGF2α. When both NO synthesis and K-channels are simultaneously blocked, inhibition of PGF2α-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.