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 aadrenoceptor blockade were studied in the isolated mesenteric artery of the rat.2 Phentolamine (32 nM) tolazoline (41 juM) and yohimbine (1.28 isM) 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 a-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 x-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 a-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 x-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 a-adrenoceptor blockade by increasing intracellular Ca2+ ion concentration or by activating a-adrenoceptor-associated Ca2+ channels.

Inotropic and Vasopressor Agents

“…The beta-2 receptors respond to circulating endogenous adrenaline or other circulating beta-2 agonists that reach the cleft by diffusion, and enhance the release of noradrenaline. Both prostaglandin and purine receptors probably inhibit noradrenaline release, although there is evidence that prostaglandin PGE2 restores noradrenergic vasoconstriction after alpha blockade (Adeagbo and Okpako, 1982).…”