MECHANISM OF NORADRENALINE POTENTIATION BY PROSTAGLANDIN E₂ IN RAT MESENTERIC ARTERY

Abstract

Effects of prostaglandins E2 and F2α (PGE2 and PGF2α) on vasoconstrictor responses to noradrenaline (NA) and methoxamine in isolated mesenteric arteries of the rat were investigated. PGE2 and to a lesser extent PGF2α potentiated vasoconstrictor responses to NA and methoxamine. Prior treatment with reserpine increased, and bretylium reduced, the extent of potentiation significantly. NA vasoconstriction persisted for 1 h after Ca2+ was removed from the perfusing Krebs solution. Prostaglandin‐induced potentiation was absent in Ca2+‐free Krebs, but increased proportionately with increase in external Ca2+ concentration. Vasoconstriction induced by high potassium, was not potentiated by PGE2. It is concluded that PGE2 potentiates NA vasoconstriction by facilitating Ca2+ influx.

Cyclo‐oxygenase inhibitors antagonize indirectly evoked contractions of the guinea‐pig isolated ileum by inhibiting acetylcholine release

“…Enhancement of the contractile power of the transmitter at the postsynaptic membrane cannot be ruled out as an additional factor in the action of PGE2. Prostaglandins of the E series are known to potentiate a variety of agonists in smooth muscles (Eagling et al, 1972;Adeagbo & Okpako, 1980;Figure 3, this study were 40-80 times more effective in blocking transmural stimulation contractions in longitudinal muscle strips, in which the diffusion barrier to Auerbach's plexus is minimal, than in whole ileum preparations (see Figure 1). Such diffusion factors may explain previous observations (Bennett et al, 1975a;Kadlec et al, 1974) showing that the inhibitory effect of indomethacin on indirectly evoked contractions of the guinea-pig ileum depended on the physiological salt solution in which the tissue was bathed.…”

“…Indeed, there is evidence that PGE2 but not PGF2a facilitates Ca2+ fluxes in smooth muscle (Eagling et al, 1972;Adeagbo & Okpako, 1980). Since PGE2-like material is released from the myenteric plexus during coaxial stimulation of the guinea-pig isolated ileum (Coceani et al, 1967;Botting & Salzmann, 1974), it may be argued that the action of cyclooxygenase inhibitors on ACh release is due to removal of a prostaglandin which normally amplifies ACh release.…”

RESTORATION OF VASOCONSTRICTOR RESPONSES TO NORADRENALINE BY PROSTAGLANDIN E2 AFTER α‐ADRENOCEPTOR BLOCKADE IN RAT ISOLATED MESENTERIC ARTERY

“…The present finding that PGE2 can restore agonist responses in the presence of a-adrenoceptor blockade without reducing the apparent affinity of the antagonist for the receptor suggests that the prostaglandin increases the availability of Ca2+ for contraction. Since restoration of NA responses can occur in normal as well as in Ca2+-free Krebs, it is possible that the action of PGE2 in this regard involves both facilitation of calcium influx (Eagling, Lovell & Piddes, 1972;Adeagbo & Okpako, 1980) and mobilization of bound intracellular Ca2+. The finding that PGE2 failed to reverse blockade caused by verapamil, cinnarizine and high concentrations of Pbz, is consistent with the view that calcium is required for the action of PGE2.…”

“…KCl-induced responses were also inhibited by cinnarizine and verapamil and PGE2 had no effect on their action. In a previous paper (Adeagbo & Okpako, 1980) (Reed & Lardy, 1972;Pressman, 1976). Like PGE2, A23187 potentiated NA vasoconstriction over a wide range of doses.…”

“…In a previous paper (Adeagbo & Okpako, 1980) adrenoceptor antagonists. This compound facilitates excitation-contraction coupling by promoting Ca2+ influx across cell membranes (Reed & Lardy, 1972;Pressman, 1976).…”