To evaluate the atrial natriuretic peptide response to angiotensin II (Ang II) infusion in non-modulating hypertension, we studied 31 men with essential hypertension. These patients were subdivided into groups of low renin patients (n=8), non-modulators (n=11), and modulators (n=12) according to their renin profile and ability to modulate renin and aldosterone responses to a graded infusion of Ang II (1.0 and 3.0 ng/kg per minute) on a low Na+ intake (10 mmol Na+ per day). During basal conditions, plasma atrial natriuretic peptide was higher (p < 0.05) in low renin patients (16.34+/-2.67 fmol/mL) than in both modulators (10.59+/-4.29 fmol/mL) and non-modulators (9.85+/-2.64 fmol/mL). During Ang II infusion, plasma atrial natriuretic peptide significantly increased in both low renin (27.67+/-2.61 fmol/mL at 60 minutes, p < 0.01) and modulating (20.36+/-3.07 fmol/mL at 60 minutes, p < 0.05) patients, whereas it did not change in non-modulators (13.94+/-4.39 fmol/mL, NS). After 5 days on a high sodium intake (200 mmol Na+ per day), plasma atrial natriuretic peptide rose in modulating (20.61+/-2.31 fmol/mL, p < 0.01 versus low sodium intake), non-modulating (20.11+/-6.48 fmol/mL, p < 0.01 versus low sodium intake), and low renin (26.13+/-3.81 fmol /mL, p < 0.00 1 versus low sodium intake) hypertensive patients. When the Ang II infusion was repeated with a high sodium intake, plasma atrial natriuretic peptide increased again in low renin and modulating patients, whereas it did not change in non-modulators. Therefore, these data indicate that an impaired atrial natriuretic peptide responsiveness to Ang II that is not dependent on Na+ intake may represent another characteristic of the non-modulating phenotype.