AJP - Heart and Circulatory Physiology, Vol 255, Issue 2 386-H393, Copyright © 1988 by American Physiological Society
Role of adenosine in noradrenergic neurotransmission
C. J. Kuan and E. K. Jackson
Department of Pharmacology, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232.
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.
