This study was designed to examine: (a) the effects of adenosine and its analogues on renin release in the absence of tubules, glomeruli, and macula densa, and (b) whether adenosine may be involved in a macula densa-mediated renin release mechanism. Rabbit afferent arterioles (Af) alone and afferent arterioles with macula densa attached (Af + MD) were microdissected and incubated for two consecutive 30-min periods. Hourly renin release rate from a single arteriole (or an arteriole with macula densa) was calculated and expressed as ng AI·h-1·Af-1 (or Af + MD-1)/h (where AI is angiotensin I). Basal renin release rate from Af was 0.69 ± 0.09 ng AI·h-1·Af-1/h(x̄±SEM, n = 16) and remained stable for 60 min. Basal renin release rate from Af + MD was 0.20 ± 0.04 ng AI·h-1·Af + MD-1/h (n = 6), which was significantly lower (P < 0.0025) than that from Af. When adenosine (0.1 μM) was added to Af, renin release decreased from 0.72 ± 0.16 to 0.24 ± 0.04 ng AI·h-1·Af-1/h (P < 0.025; n = 9). However, when adenosine was added to Af + MD, no significant change in renin release was observed. N6-cyclohexyl adenosine (an A1 adenosine receptor agonist) at 0.1 μM decreased renin release from Af from 0.69 ± 0.14 to 0.39 ± 0.12 ng AI·h-1·Af-1/h (n = 5, P < 0.05). However, 5'-N-ethylcarboxamide adenosine (an A2 adenosine receptor agonist) either at 0.1 μM or at 10 μM had no effect. Theophylline, at a concentration (10 μM) that does not block phosphodiesterase but does block adenosine receptors, increased renin release from Af + MD from 0.21 ± 0.03 to 0.46 ± 0.08 ng AI·h-1·Af + MD-1/h (P , 0.05; n = 8). The results are consistent with the hypothesis that adenosine decreases renin release via the activation of A1 adenosine receptors, and that adenosine may be an inhibitory signal from the macula densa to juxtaglomerular cells.
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