VASCULAR ACTIONS OF PURINES IN THE FETAL CIRCULATION OF THE HUMAN PLACENTA

1. The vasoactive effects of adenosine triphosphate (ATP), adenosine a nd 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 % O2:5% CO2, 37-degrees-C). Changes in foetal vascular tone were asses sed by recording perfusion pressure during constant infusion of each p urine. To allow recording of the vasodilator effects, submaximal vasoc onstriction was induced by concomitant infusion of prostaglandin F2alp ha (0.7-2.0 mumol l-1). 2 ATP (1.0-100 mumol l-1) usually caused conce ntration-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 mumol l-1) but not N(G)-nitro-D-arginine(D-NOARG)(100 mumol l-1) . They were not influenced by addition of indomethacin (10 mumol l-1) or L-arginine (100 mumol l-1). 3 Adenosine (0.0 1 - 1.0 mmol l-1) cons istently caused concentration-dependent reductions in perfusion pressu re, 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 P2y agonist was approximately 50 tim es more potent than ATP as a vasodilator agent, always causing decreas es in perfusion pressure. 5 Beta-gamma-Methylene ATP, a selective P2x agonist, was approximately 100 times more potent than ATP as a vasocon strictor, but only caused transient increases in perfusion pressure. 6 The rank order of vasodilator potencies of a selection of adenosine r eceptor agonists was, adenosine>>5-(N-cyclopropyl)-carboxamidoadenosin e, >5-N-ethylcarboxamidoadenosine, >2-chloro-N6-cyclopentyladenosine, >CGS-21680>N6-cyclohexyladenosine=adenosine. Vasodilatation due to ade nosine was inhibited by the P1-A2 receptor antagonist 3,7-dimethyl-1-p ropargylxanthine (DMPX). 7 These results suggest that ATP may cause an endothelium-dependent vasodilatation in the foetal vessels of the hum an placenta via activation of a P2y receptor linked to the formation o f nitric oxide (NO). Vasodilatation caused by ATP may mask an accompan ying vasoconstrictor effect mediated, via a P2x receptor, in the villo us vascular smooth muscle. Adenosine acting on P1-A2 receptors, which are also present in the foetal vasculature, may require synergistic in teraction with NO to achieve a maximal vasodilator response.