Evidence Against the Involvement of Prostaglandins in the Vasoconstrictor Action of Calcium Ion in Rat Mesenteric Blood Vessels

Abstract

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 pg/ml) failed to overcome the inhibitory effect of indomethacin (62 pg/ml) and ETA (10 pg/ml) on the response to the EC50 of Ca2+ (100pg/mI). The EC50 of Ca2+ did not significantly increase PGE2-like release by the blood vessels from the resting value of 19 ± 8 pg of PGE2 equivalents/min. 4 PGA, (6pg/ml) and the thromboxane A2 agonist, U-46619 (200ng/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 pg/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 Ca + in rat mesenteric blood vessels.

The activity of non-steroidal anti-inflammatory drugs in the rat mesenteric vasculature

“…All drugs depressed vasoconstrictor responses to noradrenaline and calcium, except fenbufen which did not depress responses to calcium in concentrations up to 1 mM (the limit of its solubility). The relation between their ability to depress vasoconstrictor responses to noradrenaline and calcium is statistically significant which could indicate a common mechanism of inhibition of the two agonists but this is unlikely because responses to noradrenaline that have been depressed by aspirin (Horrobin et a1 1974), indomethacin (Coupar & McLennan 1978), or meclofenamate and fenbufen (present study) are restored by PGE2, while responses to calcium that have been depressed by indomethacin are not affected (Coupar 1981). Also, noradrenaline stimulates the release of PGE2-like material which is inhibited by indomethacin, whereas calcium does not promote the release of PGEz (Coupar 1980(Coupar , 1981.…”

“…Indomethacin has been shown to inhibit responses to calcium (Northover 1968;Manku & Horrobin 1976). However, this effect does not appear to be related to inhibition of PGE2 synthesis, since the responses to calcium, that are inhibited by indomethacin, are not restored by PGE2, and calcium does not induce the release of any endogenous PGE2-like substance (Coupar 1981).…”