Four-hour infusions of synthetic atrial natriuretic peptide in normal volunteers.

Abstract

SUMMARY Two doses of synthetic atrial natriuretic peptide (0.5 and 5.0 /xg/min) and its vehicle were infused intravenously for 4 hours in eight salt-loaded normal volunteers, arid the effect on blood pressure, heart rate, renal hemodynamics, solute excretion, and secretion of vasoactive hormones was studied. The 0.5 /oig/min infusion did not alter blood pressure or heart rate, whereas the 5.0 /xg/min infusion significantly reduced the mean pressure by 20/9 mm Hg after 2.5 to 3 hours and increased the heart rate slightly. Inulin clearance was not significantly changed, but the mean p-aminohippurate clearance fell by 13 and 32% with the lower and higher doses, respectively. Urinary excretion of sodium and chloride increased slightly with the lower dose. With the higher dose, a marked increase in urinary excretion of sodium, chloride, and calcium was observed, reaching a peak during the second hour of the infusion. Potassium and phosphate excretion did not change significantly. A brisk increase in urine flow rate and fractional water excretion was seen only during the first hour of the high-dose infusion. Signs and symptoms of hypotension were observed in two subjects. No change in plasma renin activity, angiotensih II, or aldosterone was observed during either infusion, but a marked increase occurred after discontinuation of the high-dose infusion. In conclusion, the 5 /xg/min infusion induced a transient diuretic effect, delayed maximal natriuretic activity, and a late fall in blood pressure, with no change in inulin clearance but a dose-related decrease in p-aminohippurate clearance. Despite large amounts of sodium excreted arid blood pressure reduction, no coiinterregulatory changes were observed in the renin-angiotensin-aldosterone system or plasma vasopressin levels during the infusion. injections followed by a short infusion. 4 In these studies, the blood pressure effects as well as solute excretion were monitored. The peptides elicited natriuresis and diuresis 4 -8 -9 and induced a transient increase in creatinine clearance, 9 while slightly decreasing blood pressure. 8Although the triggering mechanisms and the daily profile of ANP secretion in humans are not yet known, it seems likely that a continuous infusion would yield more information on its physiological role in blood pressure regulation and renal handling of solutes than a bolus injection. We have recently evaluated the dosereponse relationship for blood pressure, heart rate, and skin blood flow during an ANP infusion lasting several hours. 10 The aim of the present study was to assess the pharmacological effect of a 4-hour infusion of synthetic ANP, at two different doses, or its vehicle on renal hemodynamics, urinary solute excretion, and plasma levels of various hormones in healthy volunteers under sodium-loaded conditions. 11-96by guest on May 10, 2018 http://hyper.ahajournals.org/ Downloaded from

Renal Hemodynamic and Natriuretic Effects of Concomitant Angiotensin-Converting Enzyme and Neutral Endopeptidase Inhibition in Men

“…2 In contrast, the administration of exogenous ANP produces no change in GFR and little or no change in effective renal plasma flow. 5 Whether dual NEP/ACE inhibitors produce a renal vasodilation and changes in GFR is less clear. Indeed, some renal vasodilation has been reported in animal models of heart failure treated with omapatrilat.…”

“…3,4 In humans, the administration of exogenous ANP and the inhibition of natriuretic peptide degradation by use of neutral endopeptidase inhibitors have been found to increase sodium and water excretion and to lower blood pressure. [5][6][7][8] Omapatrilat is a member of the new drug class of vasopeptidase inhibitors that possess the ability to inhibit the membrane-bound zinc metalloproteases ACE EC 2.4.15.1 and the neutral endopeptidase EC 3.4.24.11 (NEP). 9 Thus, omapatrilat simultaneously decreases angiotensin II generation by inhibiting ACE activity and reduces the metabolic degradation of natriuretic peptides by inhibiting NEP.…”

Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

“…Intravenous administration of ANF in normal subjects causes marked diuresis and natriuresis (9)(10)(11)(12)(13)(14), mild hypotension (12,14), and a decrease of plasma renin and aldosterone concentrations (9,12). In patients with congestive heart failure, whose plasma levels of immunoreactive ANF are elevated (9,15,16), exogenous ANF infusion improves cardiac performance by inducing peripheral vasodilation (9,17), suggesting a cardiovascular action of the peptide.…”

Vasodilatory actions of alpha-human atrial natriuretic peptide and high Ca2+ effects in normal man.

“…With the subsequent synthesis of ahANP precise investigation of the renal and vascular actions ofthis peptide in human beings has been possible. Intravenous administration of ahANP in normal subjects caused marked natriuresis and diuresis (12)(13)(14)(15)(16)(17)(18)(19)(20). But, the vasorelaxant action of this peptide has not been defined, despite the occurrence of a mild hypotension ( 15,16,19).…”