Nerve and drug-induced release of adenine nucleosides and nucleotides from rabbit aorta

The purpose of the present study was to assess the possible sites which contribute to the nerve stimulation- and alpha-agonist-induced overflow of endogenous adenine nucleosides and nucleotides in vascular tissue. Particular attention was focused on the endothelium because it is known that endothelial cells have a high concentration of ATP and its metabolites. Segments of rabbit thoracic aorta, some denuded of endothelial cells by rubbing the lumen of the vessel, were incubated in organ baths and subjected to transmural nerve stimulation or stimulated with the alpha-1 adrenoceptor agonist methoxamine. A portion of the bathing solution was processed for the determination of norepinephrine by high-performance liquid chromatography with electrochemical detection and a portion for determination of ATP, ADP, AMP and adenosine by high-performance liquid chromatography with fluorescence detection. Transmural stimulation led to a significant release of both norepinephrine and the adenine nucleosides and nucleotides in a ratio of 1 to 350. Removal of the endothelium did not change the release of norepinephrine but reduced the release of adenosine and its derivatives by 90%. Methoxamine also caused the release of adenosine and the adenine nucleotides which was reduced by 93% by removal of the endothelium. Thus, the endothelium seems to be a major source of transmural nerve stimulation and alpha-agonist induced overflow of adenosine and adenine nucleotides. The endothelium is not the exclusive source of these purine congeners, however. In the case of transmural stimulation there is approximately 10% of the total which is independent of the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)