This study was designed to examine the role of prostaglandins in the macula densa-mediated increase in plasma renin activity (PRA) during dietary sodium deprivation in rats. Micropuncture collections of early distal (ED) tubular fluid (TF) and measurements of PRA, arterial pressure (AP), and renal blood flow (RBF) were obtained in four groups of animals. Groups I and II received a normal Na diet and groups II and IV received a low Na diet; groups II and IV received indomethacin. Studies were performed after surgical denervation of the kidneys; AP and RBF were not different among the four groups of animals. EDTFna delivery was lower in groups III (0.20 +/- 0.04 neq/min) and in group IV (0.16 +/- 0.01 neq/min) animals on the low Na diet as compared with group I (0.34 +/- 0.02 neq/min) and group II (0.32 +/- 0.05 neq/min) animals on the normal Na diet. In association with the lower EDTFna delivery, the animals receiving vehicle in group III had an elevated PRA (31.46 +/- 8.81 ng/ml) as compared with group I animals on the normal Na diet receiving vehicle (4.78 +/- 1.64 ng/ml). This rise in PRA was abolished in the animals in group IV (4.06 +/- 0.81 ng/ml) that received indomethacin. We conclude that the increase in PRA, possibly resulting from macula densa receptor stimulation, during dietary Na deprivation is dependent on prostaglandin synthesis.