Restoration of vasoconstrictor responses to noradrenaline by prostaglandin E2 after alpha-adrenoceptor blockade in rat isolated mesenteric artery.
1 The effects of prostaglandin E2 (PGE2) on responses to noradrenaline (NA) after alpha-adrenoceptor blockade were studied in the isolated mesenteric artery of the rat. 2 Phentolamine (32 nM) tolazoline (41 microM) and yohimbine (1.28 microM) blocked NA-induced vasoconstriction competitively with dose-ratios of 13.9 +/- 1,22.01 +/- 1 and 26.6 +/- 0.9 respectively. 3 PGE2 (28 nM) restored responses to NA during alpha-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 alpha-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 alpha-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 alpha-adrenoceptor blockade by different mechanisms. 8 Inhibition of NA-induced vasoconstriction caused by the calcium antagonists cinnarizine, verapamil and high concentrations of phenoxybenzamine (greater than 2 nM) were not affected by PGE2. 9 It is proposed that PGE2 restores responses to NA after alpha-adrenoceptor blockade by increasing intracellular Ca2+ ion concentration or by activating alpha-adrenoceptor-associated Ca2+ channels.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004347:Drug Interactions; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D014043:Tolazoline / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011458:Prostaglandins E; D015016:Yohimbine; D000001:Calcimycin; D014043:Tolazoline; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine