Extra-natriuretic effects of atrial peptide in humans

To evaluate extra-natriuretic effects of atrial natriuretic peptide (ANP), plasma ANP (pANP) levels were assessed in seven healthy men on low-sodium diet (80 mEq NaCl/day), in basal conditions and during stepwise infusion of human ANP (2, 4, 8 and 16 ng/min/kg). To determine the individual physiological (PHY) pANP level, we measured pANP in the same subjects after a high-salt diet (400 mEq NaCl/day), that is, in a physiological stimulation of ANP. We then compared the effects of the PHY levels of ANP to the effects of pharmacological (PHA) pANP levels. Neither PHY nor PHA pANP levels modified creatinine clearance or blood pressure. The progressive rise in pANP levels was associated with increases in urinary excretion of Na+, K+ and urea. ANP alone respectively accounted for 41%, 30% and 92% of the increase in natriuresis, kaliuresis and urea excretion that occurred after changing salt intake from 80 to 400 mEq/day. Pharmacological ANP levels raised CH2O and reduced UOsm. Interestingly, PHA levels were associated with significant decrease in serum K+ (from 4.5 +/- .1 to 4.0 +/- .1 mEq/liter) and plasma urea (from 31.9 +/- 5 to 24.2 +/- 4 mg/dl). The mean cumulative urinary potassium and urea losses corresponded to the theoretical body losses of potassium and urea; moreover, the individual cumulative urinary losses of potassium and urea significantly correlated with the corresponding decrement in their plasma levels. In conclusion, ANP has both physiological and pharmacological significance in the control of potassium and urea metabolism by decreasing plasma levels of K+ and urea through effects on the renal excretory function.