Effects of adenosine receptor agonists on efferent renal nerve activity inanesthetized rats

The aim of this study was to investigate the effects of A(1) and A(2) adeno sine-receptor activation on the sympathetic nervous system. The effects on efferent renal nerve activity of selective A(1) (CCPA; 2-chloro-N-6-cyclope ntyladenosine) and A(2) (2HE-NECA; 2-hexynyl-5'-N-ethylcarboxamidoadenosine ) adenosine-receptor agonists were studied in anesthetized rats either with intact baroreflexes (intact rats) or with bilateral sinoaortic denervation and vagotomy (denervated rats). After a control period of 5 min, A(1) or A (2) agonist or vehicle were intravenously infused for 8 min in separate gro ups of intact or denervated rats, in which arterial pressure and heart rate were continuously recorded. CCPA (5.0 mu g/kg/min) and 2HE-NECA (0.7 mu g/ kg/min) were selected to obtain comparable blood pressure changes over the period of observation. Arterial pressure significantly and equally decrease d during the A(1) (-41 +/- 8%), and A(2) (-35 +/- 5%) agonist administratio n. Heart rate significantly decreased during A(1) agonist infusion, but it did not change during A(2) agonist administration. Bilateral sinoaortic den ervation and vagotomy did not modify the hemodynamic responses to both drug s. The A(1) and A(2) administration caused a large and significant increase in efferent renal nerve activity (+66 +/- 22% and +76 +/- 15%, respectivel y), and this effect was entirely abolished in denervated rats. A linear rel ation with a significant negative slope between changes in arterial pressur e and changes in neural discharge was observed for each treatment. The comp arison of the regression slopes showed that the reflex increase of efferent sympathetic activity caused by the administration of both agonists was sig nificantly smaller than the increment induced by equipotent hypotensive dos e of sodium nitroprusside (10 mu g/kg). These data show that the selective activation of A(1) and A(2) receptors elicits a reflex increase in efferent renal nerve activity. This neural activation is smaller as compared with t he effect of equihypotensive doses of sodium nitroprusside, thus indicating a blunting effect of both adenosine agonists on baroreceptor sensitivity.