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

Abstract

1 The effects of prostaglandin E₂ (PGE₂) on responses to noradrenaline (NA) after α-adrenoceptor blockade were studied in the isolated mesenteric artery of the rat. 2 Phentolamine (32 nm) tolazoline (41 μm) and yohimbine (1.28 μm) blocked NA-induced vasoconstriction competitively with dose-ratios of 13.9 ± 1, 22.0 ± 1 and 26.6 ± 0.9 respectively. 3 PGE2 (28 nm) restored responses to NA during α-adrenoceptor blockade and reduced NA dose-ratios to 2.8 ±0.1 (phentolamine), 5.9 ±0.4 (tolazoline) and 1.7 ±0.1 (yohimbine). 4 At low concentrations (0.29 nm), phenoxybenzamine blockade of NA-induced vasoconstriction was also antagonized by PGE₂. 5 PGE₂ did not reduce the pA₂ of the competitive antagonists; therefore the antagonism of α-adrenoceptor block by PGE₂ was not due to a reduction in the affinity of the antagonist for the receptor. 6 The calcium ionophore, A23187, also antagonized competitive α-adrenoceptor blockade but was less potent than PGE₂. 7 Evidence is provided to suggest that although both PGE₂ and A23187 can potentiate the action of NA in this preparation, the two compounds probably reverse α-adrenoceptor blockade by different mechanisms. 8 Inhibition of NA-induced vasoconstriction caused by the calcium antagonists cinnarizine, verapamil and high concentrations of phenoxybenzamine (>2 nm) were not affected by PGE₂. 9 It is proposed that PGE₂ restores responses to NA after α-adrenoceptor blockade by increasing intracellular Ca²⁺ ion concentration or by activating α-adrenoceptor-associated Ca²⁺ channels.