Role of Adenosine in Noradrenergic Neurotransmission

The purpose of this study was to evaluate the hypothesis that endogenous adenosine modulates noradrenergic neurotransmission in vivo during sustained periods of sympathetic nerve stimulation associated with a reduction in tissue blood flow. This hypothesis was tested in the rat mesentery in vivo by comparing the effects of periarterial (sympathetic) nerve stimulation (PNS) on mesenteric blood flow and norepinephrine (NE) spillover from the mesentery in control rats vs. rats treated with the adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX; 10 mg + 150 micrograms/min iv). In both control rats and rats pretreated with DPSPX, sustained PNS (7 Hz for 30 min) caused an initial large decrease in mesenteric blood flow and increase in NE spillover; however, these responses attenuated over the 30-min stimulation period. The time course of PNS-induced changes in mesenteric blood flow and NE spillover were not altered by treatment with DPSPX. However, administration of DPSPX prevented inhibition of noradrenergic neurotransmission in the rat mesentery by 2-chloroadenosine, which indicated that an effective level of DPSPX was achieved. We conclude that even during sustained sympathetic nerve stimulation associated with reductions in tissue perfusion, endogenous adenosine does not modulate noradrenergic neurotransmission in vivo in the rat mesentery.