Haemodynamic and renal tubular responses to low-dose infusion or bolus injection of the peptide ANF in anaesthetized rats.

1. Renal haemodynamic and tubular transport responses to low-dose infusions (0.1-5.0 ng min-1) and injections (50-200 ng) of atrial natriuretic factor (ANF) were studied in anaesthetized rats (average body weight, 300 g). 2. The lowest infusion dose (average, 0.3 ng kg-1 min-1) was above threshold for significant hypotension (-11 mmHg), increased glomerular filtration (20%), urine flow (104%) and sodium output (191%). 3. Compared with the lowest rate of infusion of ANF, the smallest injection dose (50 ng) was less effective in reducing blood pressure, caused no change in glomerular filtration rate but induced similar diuresis and natriuresis. Based on total dose administered, sensitivity to injection was only one-tenth that of infusion. 4. Absolute proximal reabsorption, derived from lithium clearance measurements, did not increase in parallel with filtration rate during infusions, and fractional proximal reabsorption was markedly depressed. Proximal glomerulo-tubular balance was only 50% effective at 0.1 ng min-1, falling to 16% at 5 ng min-1. 5. Despite complete recovery of filtration rate and filtration fraction 30 min after terminating infusions, diuresis, natriuresis and depressed fractional proximal reabsorption persisted. Time-control animals displayed no changes in renal function. 6. It is proposed that disruption of glomerulo-tubular balance occurred in these experiments from inhibition of endogenous angiotensin II-stimulated proximal sodium reabsorption by ANF. Persistence of this action may be due to accumulation of intracellular messengers or to sequestration of biologically active ANF bound to 'clearance receptors'.