The present studies were performed to assess, in the isolated perfused juxtaglomerular apparatus of the rabbit kidney, the effect of exogenous adenosine on renin secretion stimulated by a low NaCl concentration at the macula densa. Addition of adenosine to the bath resulted in a change of renin secretion from 30.4 to 23.9 nGU/min at an adenosine concentration of 10(-6) M (n = 7; P = NS), from 38.6 to 17.9 nGU/min at a concentration of 10(-4) M (n = 7; P = 0.038), and from 18.4 to 5.8 nGU/min at 10(-2) M (P = 0.0053). Addition of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-5) M fully reversed the effect of adenosine at 10(-4) M, but not at 10(-2) M. Inhibition of adenosine breakdown by the adenosine deaminase inhibitor pentostatin (10(-6) M) enhanced the inhibitory effect of adenosine with renin secretion falling from 61.7 to 19.5 nGU/min at 10(-6) M adenosine (P = 0.035) and from 44.7 to 13.5 nGU/min at 10(-4) M adenosine (n = 0.027). A marked inhibition of NaCl-dependent renin secretion was caused by both angiotensin II (P = 0.011) and angiotensin III (P = 0.006), both at 10(-8) M. These results show that adenosine is capable of reducing macula densa-mediated renin secretion, but that this effect, even at very high concentrations or during adenosine deaminase blockade, does not fully mimic the inhibitory potency of increasing luminal NaCl concentration. Because the marked effect caused by angiotensins establishes the potential of this preparation to demonstrate inhibitory hormonal influences, it is concluded that adenosine does not appear to be the sole paracrine factor responsible for the NaCl-induced reduction of renin secretion.