In cascade perfusion and superfusion experiments on rabbit tissues, when acetylcholine (ACh) was introduced into the circuit so as to perfuse the aorta under perfusion with noradrenaline (NA), the effluent relaxed the transverse aortic strip which had been denuded of endothelium. The effluent from the perfused aorta which was capable of relaxing the transverse aortic strip also significantly inhibited platelet aggregation induced by arachidonic acid (AA) in a volume‐related manner. The inhibitory activity was decreased by the prolongation of transit time before addition of the effluent to platelet‐rich plasma. Neither the inhibition of AA‐induced aggregation nor the relaxation of the transverse strip by the effluent could be observed after the removal of endothelium from the aorta, or after pretreatment of aorta with mepacrine or nordihydroguaiaretic acid (NDGA). The AA‐induced platelet aggregation was unaffected by pretreatment of platelets with mepacrine or NDGA at the concentration tested. Pretreatment of aorta with indomethacin failed to modify the relaxation of the transverse strip induced by the effluent. These results strongly suggest that endothelium‐derived vascular relaxant factor (EDRF) possesses inhibitory activity on AA‐induced aggregation in addition to its vasodilator activity.

Seven novel polyhydroxylated steroids were isolated from the nucho-dorsal glands of the snake, Rhabdophis tigrinus. Biological activities of these steroids in inhibiting (Na+ + K+)ATPase and in producing positive inotropic action were examined in comparison with those of ouabain and gamabufotalin. Gamabufotalin was approximately 10 times more potent than ouabain in inhibiting (Na+ + K+)ATPase. Two compounds, compounds III and XIII, of the seven, produced nearly equipotent enzyme inhibitory activity to ouabain. The activity of the remaining five was relatively low among the compounds tested. All compounds exhibited more or less positive inotropic action in the papillary muscle preparations. The ranking order of the potency was: gamabufotalin greater than ouabain and compound IV greater than compound III and XIII greater than compound I, II, XII and XIV.

1 The purpose of the present experiments was to investigate the pharmacological mechanisms of the vasoconstriction caused by the toxin (pCrTX) which had been partially purified from the tentacles of the jellyfish Carybdea rastonii ('Andonkurage').2 pCrTX (0.1 to 10 ptg ml'-l) produced a tonic contraction of rabbit aortic strips, which was nearly abolished in Ca2+-free medium and was significantly reduced by verapamil or diltiazem. 3 pCrTX stimulated 45Ca2+-influx and this effect was markedly attenuated by verapamil. 4 pCrTX-induced vasoconstriction was significantly attenuated by phentolamine, 6-hydroxydopamine (6-OHDA) and in low Na'-medium, but not by bretylium, guanethidine, reserpinization or tetrodotoxin (TTX). 5 pCrTX continuously and significantly increased the 3H-efflux from [3H1-noradrenaline preloaded aortic strips and this effect was completely inhibited by pretreatment with 6-OHDA and in Ca2+-free medium, but not by phentolamine, bretylium, guanethidine or TTX.6 A single exposure to pCrTX for 30min greatly reduced the contractile responses to tyramine, nicotine and transmural electrical stimulation, but not those to noradrenaline or KC1. In addition, incorporation of [3HJ-noradrenaline was reduced.7 Pretreatments with chlorphenylamine or indomethacin failed to modify the contractile response to pCrTX. 8 These results suggest that the pCrTX-induced vasoconstriction is caused by a presynaptic action, releasing noradrenaline from the intramural adrenergic nerve terminals, and by a postsynaptic action, which consists at least in part of stimulation of the transmembrane calcium influx. Both pre-and postsynaptic actions depend on the external calcium concentration. The data further suggest that pCrTX damages the noradrenaline uptake and/or storage mechanisms without damaging postsynaptic contractile systems.

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4-Aryl derivatives of 7-ethoxycarbonyl-6,8-dimethyl-1(2H)-phthalazinone and related derivatives were newly synthesized in order to test for their inhibitory activities on platelet aggregation. 4-(2-Anisyl) compound and the corresponding 1-chloro derivative demonstrated significant activity.