Hemodynamic, renal, and endocrine effects of 4-h infusions of human atrial natriuretic peptide in normal volunteers.

Summary— A synthetic human atrial natriuretic peptide of 26 aminoacids [human (3–28)ANP or hANP] was infused into normal male volunteers. Six subjects were infused for 4 h at 1-wk intervals with either hANP at the rate of 0.5 or 1.0 μg/min or its vehicle in a single-blind randomized order. Human (3–28)ANP at the dose of 0.5 μg/min raised immunoreactive plasma ANP levels from 104 ± 17 to 221 ± 24 pg/ml (mean ± SEM), but it induced no significant change in blood pressure, heart rate, effective renal plasma flow, glomerular filtration rate, or renal electrolyte excretion. At the rate of 1.0 μg/min, human (3–28)ANP increased immunoreactive plasma ANP levels from 89 ± 12 to 454 ± 30 pg/ml. It reduced effective renal plasma flow from 523 ± 40 to 453 ± 38 ml/min (P<0.05 vs. vehicle), but left glomerular filtration rate unchanged. Natriuresis rose from 207±52 to 501±69 μmol/min (P<0.05 vs. vehicle) and urinary magnesium excretion from 3.6±0.5 to 5.6±0.5 μmol/min (P<0.01 vs. vehicle). The excretion rate of the other electrolytes, blood pressure, and heart rate were not significantly modified. At both doses, human (3–28)ANP tended to suppress the activity of the renin-angiotensin-aldosterone system. In 3 additional volunteers, the skin blood flow response to human (3–28)ANP, infused for 4 h at the rate of 1.0μg/min, was studied by means of a laser-doppler flowmeter. The skin blood flow rose during the first 2 h of pep-tide administration, then fell progressively to values below baseline. After the infusion was discontinued, it remained depressed for more than 2 h. Thus, in normal volunteers, human (3–28)ANP at the dose of 1.0 μg/min produced results similar to those obtained previously with rat (3–28)ANP. It enhanced natriuresis without changing the glomerular filtration rate while effective renal plasma flow fell. It also induced a transient vasodilation of the skin vascular bed.