Unilateral nephrectomy (UNX) is associated with an immediate and transient increase in arterial pressure and in prompt natriuresis from the remaining kidney. The hypothesis that atrial natriuretic peptide (ANP) is involved in the acute adaptation to unilateral nephrectomy was tested in euvolemic anesthetized Sprague-Dawley rats. In a first series of experiments, an increase in circulating ir-ANP levels (from 23.5 +/- 3.6 to 66.3 +/- 12.8 fmol/ml; p less than 0.01) was found within 2 minutes following renal exclusion. In a second set of experiments, the ANP response was inhibited by performing a right atrial appendectomy, in order to eliminate the major source of ANP, or by intravenous administration of monoclonal antibodies directed against ANP. When UNX was performed in the control groups (sham atrial appendectomy and administration of non specific monoclonal antibodies), mean arterial pressure rose immediately (maximal about 12% within 4 minutes) and transiently (return to pre-UNX values within 20 minutes) after UNX. At the same time, central venous pressure, monitored in the right atrium, tended to decrease slightly. In rats pretreated by right atrial appendectomy or by monoclonal antibodies directed against ANP, arterial pressure increased to the same extent as observed in control groups; this increase however was significantly more prolonged. In control groups, urinary cGMP excretion, the biological marker of ANP, increased twofold in parallel with the natriuretic response. These two responses were blunted in right atrial appendectomized rats and in rats receiving antibodies against-ANP. These results suggest that atrial natriuretic peptide plays a major role in the immediate functional adaptation to unilateral nephrectomy by blunting the increase in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)