Effects of adenosine triphosphate and prostaglandins on vascular adrenergic transmission

The effects of prostaglandins (PGs) on the adrenergic neuroeffector transmission and their relationship to the action of ATP were investigated. This was in view of the putative negative feedback mediated by ATP or a related purine compound, and the reported stimulation of PG synthesis by adenine nucleotides. The central ear artery and saphenous vein of the rabbit were isolated and their contractile responses to adrenergic nerve stimulation monitored. These responses were markedly reduced by PGE1 and PGE2 and significantly augmented by indomethacin and aspirin, suggesting the occurrence of the PGE-mediated negative feedback. PGF2a facilitated the response of the vein but was without affect on the artery, while arachidonic acid was facilitatory on the former and inhibitory on the latter. Possibly a PGF2a-like substance is formed in the presence of arachidonic acid and, in the vein, masks the effect of any PGE. ATP depressed the arterial and venous contractile response to adrenergic nerve stimulation. This inhibition was not significantly affected by indomethacin or aspirin. It was enhanced in the artery and diminished in the vein by arachidonic acid, but only to the extent of algebraic sum of the effects of ATP and the acid. It seems possible that the purine- and PGE-mediated feedback mechanisms are independent and parallel pathways.