Presynaptic inhibition of sympathetic neurotransmission by adenosine in the rat kidney

The effect of adenosine on responses to sympathetic nerve stimulation was studied in the isolated perfused rat kidney. Adenosine at 1, 3 and 10 micrograms/ml caused significant impairment of renal sympathetic neurotransmission as evidenced in a dose-dependent reduction in the vasoconstrictor responses elicited by periarterial nerve stimulation at 2, 4 and 8 Hz. Vasoconstriction to exogenous norepinephrine was unaffected by adenosine except at 10 micrograms/ml where there was a slight reduction in response to norepinephrine. Theophylline, an adenosine receptor antagonist, inhibited the above action of adenosine at the frequencies of 2 and 4 Hz. At 2 Hz, 10 microM theophylline completely blocked the effect of 1 and 3 micrograms/ml adenosine and reduced by 50% the inhibitory action of 10 micrograms/ml. Higher concentration of theophylline (50 microM) was required to antagonize the action of adenosine at 4 Hz. These results indicate that adenosine can inhibit sympathetic neurotransmission in the rat kidney through a presynaptic purinergic mechanism. The physiological and pharmacological significance of this presynaptic action of adenosine is discussed.