Effects of p-aminohippurate and pyrazinoate on the renal excretion of salicylate in the rat: a micropuncture study.

The inhibitory effects of p-aminohippurate and pyrazinoate (PZA) on the transport of salicylate were studied by free-flow micropuncture in the rat. p-Aminohippurate (5, 10 or 25 mumol/kg X min) and PZA (10 or 25 mumol/kg X min) inhibited proximal tubular secretion of salicylate; they induced decreases in the fractional delivery of salicylate to the late proximal tubules. In alkalotic rats, the late proximal decrease in fractional delivery of salicylate was accompanied by a decreased fractional excretion of salicylate. In contrast, such a decrease in fractional excretion of salicylate was not observed in rats in normal acid-base balance. A greater rate of PZA infusion (25 mumol/kg X min) not only inhibited secretion, but also depressed a reabsorptive carrier-mediated transport of salicylate. Thus, in alkalotic rats, fractional delivery of salicylate to late proximal tubules were 1.90 +/- 0.15, 0.90 +/- 0.10 and 1.34 +/- 0.13, respectively, for control rats and rats infused with 10 or 25 mumol/kg X min of PZA. The corresponding values of fractional excretion of salicylate were 1.21 +/- 0.09, 0.61 +/- 0.05 and 0.08 +/- 0.09, respectively. The data suggest that salicylate is secreted as well as reabsorbed by carrier-mediated mechanisms and that there may be two secretory mechanisms.