Evidence against the involvement of prostaglandins in the vasoconstrictor action of calcium ion in rat mesenteric blood vessels.

1. Prostaglandin E2 (PGE2) has been claimed to be essential to the vasoconstrictor action of noradrenaline in rat mesenteric blood vessels. Since noradrenaline acts by releasing intracellular calcium, experiments have been performed using the perfused rat superior mesenteric artery preparation to determine whether prostaglandin synthesis is necessary for the direct vasoconstrictor action of calcium. 2. The cyclo-oxygenase inhibitors, indomethacin and 5,8,11,14-eicosatetraynoic acid (ETA), inhibited responses to noradrenaline and calcium but both were less effective in inhibiting the response to calcium than to noradrenaline. 3. PGE2 (6 ng-20 micrograms/ml) failed to overcome the inhibitory effect of indomethacin (62 micrograms/ml) and ETA (10 micrograms/ml) on the response to the EC50 of Ca2+ (100 micrograms/ml). The EC50 of Ca2+ did not significantly increase PGE2-like release by the blood vessels from the resulting value of 19 +/- 8 pg of PGE2 equivalents/min. 4. PGA1 (6 micrograms/ml) and the thromboxane A2 agonist, U-46619 (200 ng/ml), both caused full restoration of indomethacin-depressed responses to calcium, but did not restore responses depressed by ETA. U-46619 (200 ng/ml) also reversed the inhibitory effect of papaverine (4 micrograms/ml) and caused a 1.6 fold potentiation of Ca2+ responses. 5. The results do not support the hypothesis that prostaglandin synthesis is essential to the vasoconstrictor action of Ca2+ in rat mesenteric blood vessels.