Atrial natriuretic peptide and dopamine in a rat model of ischemic acute renal failure. Atrial natriuretic peptide (ANP) has been shown to reverse experimental models of ischemic acute renal failure (ARF). However, infusion of ANP has been associated with systemic hypotension making its use in clinical ARF impractical. Therefore, in this investigation, dopamine (D) was combined with intravenous (i.v.) atriopeptin III (AP III) to determine if this regimen was effective in reversing ARF while preventing systemic hypotension and maintaining renal blood flow (RBF). Four groups of Munich-Wistar rats were studied. Group 1, sham-ARF; Group 2, renal artery (RA) clamp (55 min) followed by i.v. saline; Group 3, RA clamp followed by i.v. AP III-D; and Group 4, RA clamp followed by i.v. D only. All infusions were begun after RA clamp release and continued for four hour. Mean arterial pressure in Group 3 rats given AP III-D were similar to that in Group 2, slightly less than that in Groups 1 and 4 (P < 0.05), but consistently > 100 mm Hg during the four hour infusion. RBF in Group 3 was elevated above the level in Group 1 at P < 0.05. Glomerular filtration rate (GFR), depressed by 52% in Group 2, was corrected to control (sham-ARF) levels in Group 3. In Group 4 there was a small but significant increase in GFR compared to Group 2 (P < 0.05), but it remained less than that in sham-ARF or AP III-D treated ARF rats (P < 0.01). Urine flow rate and urine sodium excretion rate were more than sixfold higher in Group 3 than any other group. Micropuncture measurements revealed single nephron glomerular filtration rate (SNGFR) in Group 3 to be twice that in Group 2 and actually greater than sham-ARF rats (P < 0.05), while it remained similar to Group 2 in the Group 4 rats. The increase in SNGFR in the APIII-D treated ARF rats was due to marked increases in both glomerular capillary hydraulic pressure (P_GC) and glomerular plasma flow rate (Q_A) as the result of a major decline in afferent arteriolar resistance (R_A) compared to the other three groups. It was concluded that the combination of i.v. AP III and D is effective in restoring GFR in an ischemic model of ARF while preventing systemic hypotension and maintaining RBF. The dominant effect on glomerular hemodynamics, attributable primarily to AP III, was a reduction in R_A causing striking increases in both P_GC and Q_A.