Adenosine affects sympathetic neurotransmission at multiple sites in vivo

We examined the effects of adenosine and its analogs on sympathomimetic responses of pithed rats to electrical stimulation of preganglionic sympathetic nerves (ES) or to injections of nicotine, phenylephrine (PE) or isoproterenol (ISO). Four physiological indices of sympathetic neurotransmission were measured: blood pressure, heart rate and contractions of smooth muscle in vas deferens and eyelid. Elevation of arterial adenosine levels from 1.5 to 2 to 3 microM caused a 2- to 3-fold potentiation of nicotine-induced increases in blood pressure, heart rate and smooth muscle tension. Higher adenosine concentrations (3-4 microM) produced a smaller potentiation of the effects of nicotine. At 2 to 3 microM, adenosine had no effect on sympathomimetic responses to ES or PE. Higher concentrations (3-4 microM) attenuated pressor responses to ES and PE and the contractile responses of the vas deferens to ES; these levels also potentiated positive chronotropic responses to ISO. The adenosine analogs N-cyclopropylcarboxamido adenosine (N-CPCA), 2-chloroadenosine (2-CLA) and R- and S-phenylisopropyl adenosine (R-PIA and S-PIA) also reduced pressor responses to both ES and PE, with the potency order: N-CPCA greater than R-PIA greater than 2-CLA greater than S-PIA. These analogs exhibited this same potency series in attenuating contractile responses to ES in the vas deferens. However, all four analogs potentiated, at the lower doses tested, the contractile response of the vas deferens to PE; at higher concentrations, inhibition predominated. N-CPCA enhanced the chronotropic effects of ISO and ES.(ABSTRACT TRUNCATED AT 250 WORDS)