Premium
RESTORATION OF VASOCONSTRICTOR RESPONSES TO NORADRENALINE BY PROSTAGLANDIN E 2 AFTER α‐ADRENOCEPTOR BLOCKADE IN RAT ISOLATED MESENTERIC ARTERY
Author(s) -
ADEAGBO A.S.O.,
OKPAKO D.T.
Publication year - 1982
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1982.tb08756.x
Subject(s) - phenoxybenzamine , phentolamine , yohimbine , tolazoline , vasoconstriction , verapamil , endocrinology , blockade , medicine , chemistry , pharmacology , propranolol , antagonist , calcium , receptor
1 The effects of prostaglandin E 2 (PGE 2 ) on responses to noradrenaline (NA) after α‐adrenoceptor blockade were studied in the isolated mesenteric artery of the rat. 2 Phentolamine (32 n m ) tolazoline (41 μ m ) and yohimbine (1.28 μ m ) blocked NA‐induced vasoconstriction competitively with dose‐ratios of 13.9 ± 1, 22.0 ± 1 and 26.6 ± 0.9 respectively. 3 PGE2 (28 n m ) 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 n m ), phenoxybenzamine blockade of NA‐induced vasoconstriction was also antagonized by PGE 2 . 5 PGE 2 did not reduce the pA 2 of the competitive antagonists; therefore the antagonism of α‐adrenoceptor block by PGE 2 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 PGE 2 . 7 Evidence is provided to suggest that although both PGE 2 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 n m ) were not affected by PGE 2 . 9 It is proposed that PGE 2 restores responses to NA after α‐adrenoceptor blockade by increasing intracellular Ca 2+ ion concentration or by activating α‐adrenoceptor‐associated Ca 2+ channels.