The influence of prostaglandins on noradrenaline-induced vasoconstriction in isolated perfused mesenteric blood vessels of the rat

摘要

>1 The report of the depression by indomethacin of vasoconstrictor responses to noradrenaline and their partial restoration by prostaglandin E2 (PGE2) and PGE1 in rat isolated perfused mesenteric blood vessels was investigated. The further suggestion that prostaglandins may be necessary for the combination of noradrenaline with the α-adrenoceptor in this tissue was also studied.>2 The reported depression by indomethacin was confirmed and was further shown to be in the form of a concentration-dependent flattening of the noradrenaline concentration-effect curve.>3 A concentration-dependent restorative effect was observed for all prostaglandins studied. The decreasing order of potency for the restoration towards normal of the indomethacin-depressed responses to noradrenaline was: PGE2, PGE1, PGA1, PGF2α, PGA2.>4 The prostaglandins studied were not uniform in their restorative actions and could be separated into two groups. PGE2 and PGE1 restored responses towards the control level whereas PGA1, PGA2 and PGF2α increased responses to an above control level and did so over a smaller concentration range. The possibility of several prostaglandin receptors is discussed.>5 At concentrations equi-effective in restoring depressed responses to control levels PGA1 but not PGE2, caused a parallel shift of the noradrenaline concentration-effect curve to the left and a small, gradual rise in the basal perfusion pressure.>6 The reason for the differing effects remains obscure but does not seem to involve a change in the α-adrenoceptor as indicated by the pA2 of phentolamine. Furthermore, the restorative and potentiating effect of PGA₁ is not mediated by blockade of neuronal uptake of noradrenaline.>7 It appears that prostaglandins are required for the vasoconstrictor action of noradrenaline in rat mesenteric blood vessels and that this effect is distal to the drug-receptor interaction. The possible involvement of prostaglandins with intracellular calcium ions is discussed.