Clinical pharmacology of atrial natriuretic (3-28) eicosahexapeptide.
The clinical pharmacology of a synthetic rat atrial natriuretic peptide (rANP) was evaluated in normal volunteers. During a dose-ranging study at 1-40 micrograms/min we observed a dose-dependent decrease in mean intra-arterial blood pressure, an acceleration of the heart rate and a transient increase in blood flow to the skin. During a 4-h constant-dose infusion at 0.5 and 5.0 micrograms/min, inulin clearance remained unchanged but there was a dose-related fall in paraaminohippurate (PAH) clearance and an increase in the filtration fraction. Urinary excretion of sodium, chloride and calcium increased in a dose-related fashion, but with the high dose the excretion curve had a bell-shape. No change in plasma renin activity, angiotensin II and aldosterone was observed during the rANP infusion despite the excretion of large amounts of sodium and a blood pressure reduction with the high dose. Indocyanine green clearance, a measure of hepatic blood flow, was significantly decreased by a 2-h rANP infusion at 1.0 microgram/min. In normal volunteers, therefore, rANP induced vasodilation and blood pressure reduction, a decrease in renal and hepatic blood flow and a natriuretic and transient diuretic effect without activation of the renin-angiotensin-aldosterone system.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000494:pharmacology*; D010710:Phosphates / Q000652:urine; D011188:Potassium / Q000652:urine; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors
D010446:Peptide Fragments; D010710:Phosphates; C049490:atrial natriuretic factor (3-28); D009320:Atrial Natriuretic Factor; D011188:Potassium; D002118:Calcium