Renal, Hemodynamic, and Hormonal Responses to Atrial Natriuretic Peptide Infusions in Normal Man, and Effect of Sodium Intake*

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Abstract
The effect of 60-min constant iv infusions of αhuman atrial natriuretic peptide (αhANP; 200 μg), sufficient to increasethe steady state venous plasma αhANP concentration to levels found inpatients with some circulatory disorders, was studied in six normal men equilibrated on a high sodium diet (200 mmol daily) and again when equilibrated on a low sodium intake (10 mmol daily). In each instance, the responsestoαhANP were compared to those to control infusions given on the preceding day. The mean steady state plasma immunoreactive ANP concentration during the infusions was 320 pmol/liter and was the same during both diets. Thus, the MCR of αhANP was unaffected by major changes in sodium intake. Compared to control day observations, infusions of ahANP induced a more than 3-fold increase in sodium excretion and at least a 2-fold increase in urine volume and calcium and magnesium excretion in subjects ingesting 200 mmol sodium daily. During the low sodium diet, αhANP was still diuretic and induced comparable magnesium excretion, but the natriuresis was only 11% of that during the high salt diet. No significant changes in blood pressure or heart rate occurred during αhANP infusions during either diet, although during both diets there was a significant rise in plasma norepinephrine (P < 0.02), which persisted well beyond the disappearance of immunoreactive ANP from plasma. Despite this sympathetic activation, renin and aldosterone production was reduced by αhANP. During low salt intake, αhANP significantly decreased PRA (mean pretreatment, 1.79; posttreatment, 1.25 nmol/liter/h; P < 0.03), angiotensin II (mean pretreatment, 49; posttreatment, 28 pmol/liter; P < 0.008), and plasma aldosterone (mean pretreatment, 554; posttreatment 307 pmol/liter; P < 0.007), whereas values during control infusions did not change. Similar percent decreases in PRA and aldosterone also occurred during the high salt diet. Plasmacortisol and arginine vasopressin did not change during the ahANP infusionson either diet. We conclude that steady state levels of αhANP in plasma, similar to those in patients with some circulatory disorders, significantly increasesodium excretion and inhibit all elements of the renin-angiotensin-aldosterone system. The natriuretic, but not the hormonal or chronotropic, effects of αhANP are reduced by sodium depletion in normal man.