THE ACTION OF ATRIOPEPTIN-III ON RENAL-FUNCTION IN 2 MODELS OF CHRONIC-RENAL-FAILURE IN THE RAT

1. The natriuretic and diuretic effects of atriopeptin III (125, 250 and 500 ng kg-1, i.v.) were studied in groups of rats anaesthetized with pentobarbitone which were either sham controls, unilaterally nephrectomized controls, adenine-fed or subtotal nephrectomy chronic renal failure models. 2. Atriopeptin III given at these doses to the sham control animals had no effect on blood pressure, renal blood flow or glomerular filtration rate but reversibly increased urine flow, between 46% to 54%, absolute sodium excretion, between 52% to 61%, and fractional sodium excretion, between 48% to 54% (all P values <0.05) from the lowest to the highest dose. The adenine-fed chronic renal failure group of rats had a reduced renal blood flow between 30 and 75%, and glomerular filtration rate of approximately 20%, compared to the sham controls. Administration of atriopeptin at 125, 250 and 500 ng kg-1 to the animals with renal failure increased water and sodium excretion to the same degree as observed in the sham group of rats. 3. In the group of unilaterally nephrectomized rats, atriopeptin III, at 125, 250 and 500 ng kg-1 increased urine flow by 36%, 47% and 72%, respectively, absolute sodium excretion by 37%, 57% and 106%, respectively, and fractional sodium excretion by 46%, 45% and 102%, respectively. A similar pattern of responses was observed in the subtotal nephrectomy, chronic renal failure group in which filtration rate was approximately 4 times less than the controls. Although the magnitude of the urine flow and absolute sodium excretion responses were the same, the increases in fractional sodium excretion were all significantly larger than in the unilaterally nephrectomized control group. 4. These results show that in two different models of chronic renal failure, atriopeptin III still caused a natriuresis and diuresis. This suggests that the nephrons retain sensitivity to the atrial natriuretic peptides in diseases such as chronic renal failure and that these compounds may be useful in mobilizing body fluids in this situation.