The effect of a synthetic atrial natriuretic peptide (atriopeptin III) on blood pressure, heart rate, and hematocrit was investigated in conscious, nephrectomized (n = 6), and sham-operated (n = 6) rats. Atriopeptin III infusion (1 microgram/min iv for 30 min) decreased mean blood pressure to a similar extent in nephrectomized [from 122 +/- 5 to 108 +/- 3 (SE) mmHg; P less than 0.01] and in sham-operated rats (from 124 +/- 4 to 103 +/- 2 mmHg; P less than 0.01), whereas it had no significant effect on heart rate. Hematocrit rose similarly in nephrectomized (from 45 +/- 1 to 49 +/- 1%; P less than 0.01) and in sham-operated rats (from 46 +/- 1 to 50 +/- 1%; P less than 0.001). Infusion of the vehicle of atriopeptin III to nephrectomized rats (n = 7) did not change any of these parameters. Plasma volume and red cell mass of nephrectomized rats infused with atriopeptin III was measured by use of radiolabeled albumin and erythrocytes, respectively. A plasma volume contraction of approximately 10% (P less than 0.01) was observed, whereas red cell mass did not change. In an additional group of nephrectomized rats (n = 6), Na nitroprusside was infused intravenously at a rate of 2 micrograms/min for 30 min. Na nitroprusside reduced mean blood pressure from 127 +/- 4 to 106 +/- 3 mmHg (P less than 0.001), but hematocrit remained unchanged (46 +/- 1% before vs. 45 +/- 1% after infusion). In four anesthetized rats with both kidneys and the spleen removed atriopeptin III still raised the hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)