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Vascular actions of purines in the foetal circulation of the human placenta
Author(s) -
Read M.A.,
Boura A.L.A.,
Walters W.A.W.
Publication year - 1993
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.1476-5381.1993.tb13832.x
Subject(s) - vasodilation , perfusion , adenosine , vasoconstriction , nitroarginine , endocrinology , medicine , chemistry , arginine , placenta , potency , fetus , nitric oxide , biology , biochemistry , nitric oxide synthase , in vitro , pregnancy , amino acid , genetics
1 The vasoactive effects of adenosine triphosphate (ATP), adenosine and other purines in the foetal circulation of the human placenta were examined. Single lobules of the placenta were bilaterally perfused in vitro with Krebs buffer (maternal and foetal sides 5 ml min −1 each, 95% O 2 :5% CO 2 , 37°C). Changes in foetal vascular tone were assessed by recording perfusion pressure during constant infusion of each purine. To allow recording of the vasodilator effects, submaximal vasoconstriction was induced by concomitant infusion of prostaglandin F 2α (0.7–2.0 μmol 1 −1 ). 2 ATP (1.0–100 μmol 1 −1 ) usually caused concentration‐dependent reductions in perfusion pressure. However, biphasic with initial transient increases, or only increases in pressure were sometimes observed. Falls in pressure caused by ATP were significantly reduced by addition to the perfusate of N G ‐nitro‐ l ‐arginine ( l ‐NOARG) (100 μmol 1 −1 ) but not N G ‐nitro‐ d ‐arginine ( d ‐NOARG) (100 μmol 1 −1 ). They were not influenced by addition of indomethacin (10 μmol 1 −1 ) or l ‐arginine (100 μmol 1 −1 ). 3 Adenosine (0.01–1.0 mmol 1 −1 ) consistently caused concentration‐dependent reductions in perfusion pressure, this effect not being influenced by indomethacin. l ‐NOARG, but not d ‐NOARG, reduced the potency of adenosine approximately three fold. l ‐Arginine, but not d ‐arginine enhanced its potency by a similar amount. 4 2‐Methylthio‐ATP, a selective P 2y agonist was approximately 50 times more potent than ATP as a vasodilator agent, always causing decreases in perfusion pressure. 5 β‐γ‐Methylene ATP, a selective P 2x agonist, was approximately 100 times more potent than ATP as a vasoconstrictor, but only caused transient increases in perfusion pressure. 6 The rank order of vasodilator potencies of a selection of adenosine receptor agonists was, 2‐chloroadenosine >> 5‐(N‐cyclopropyl)‐carboxamidoadenosine, >5‐N‐ethylcarboxamidoadenosine, >2‐chloro‐N 6 ‐cyclopentyladenosine, >CGS‐21680 > N 6 ‐cyclohexyladenosine = adenosine. Vasodilatation due to adenosine was inhibited by the P 1 ‐A 2 receptor antagonist 3,7‐dimethyl‐1‐propargylxanthine (DMPX). 7 These results suggest that ATP may cause an endothelium‐dependent vasodilatation in the foetal vessels of the human placenta via activation of a P 2y receptor linked to the formation of nitric oxide (NO). Vasodilatation caused by ATP may mask an accompanying vasoconstrictor effect mediated, via a P 2x receptor, in the villous vascular smooth muscle. Adenosine acting on P 1 ‐A 2 receptors, which are also present in the foetal vasculature, may require synergistic interaction with NO to achieve a maximal vasodilator response.